WorldWideScience

Sample records for associative cerebral cortex

  1. Reorganization of the somatosensory cortex in hemiplegic cerebral palsy associated with impaired sensory tracts.

    Science.gov (United States)

    Papadelis, Christos; Butler, Erin E; Rubenstein, Madelyn; Sun, Limin; Zollei, Lilla; Nimec, Donna; Snyder, Brian; Grant, Patricia Ellen

    2018-01-01

    Functional neuroimaging studies argue that sensory deficits in hemiplegic cerebral palsy (HCP) are related to deviant somatosensory processing in the ipsilesional primary somatosensory cortex (S1). A separate body of structural neuroimaging literature argues that these deficits are due to structural damage of the ascending sensory tracts (AST). The relationship between the functional and structural integrity of the somatosensory system and the sensory performance is largely unknown in HCP. To address this relationship, we combined findings from magnetoencephalography (MEG) and probabilistic diffusion tractography (PDT) in 10 children with HCP and 13 typically developing (TD) children. With MEG, we mapped the functionally active regions in the contralateral S1 during tactile stimulation of the thumb, middle, and little fingers of both hands. Using these MEG-defined functional active regions as regions of interest for PDT, we estimated the diffusion parameters of the AST. Somatosensory function was assessed via two-point discrimination tests. Our MEG data showed: (i) an abnormal somatotopic organization in all children with HCP in either one or both of their hemispheres; (ii) longer Euclidean distances between the digit maps in the S1 of children with HCP compared to TD children; (iii) suppressed gamma responses at early latencies for both hemispheres of children with HCP; and (iv) a positive correlation between the Euclidean distances and the sensory tests for the more affected hemisphere of children with HCP. Our MEG-guided PDT data showed: (i) higher mean and radian diffusivity of the AST in children with HCP; (ii) a positive correlation between the axial diffusivity of the AST with the sensory tests for the more affected hemisphere; and (iii) a negative correlation between the gamma power change and the AD of the AST for the MA hemisphere. Our findings associate for the first time bilateral cortical functional reorganization in the S1 of HCP children with

  2. Cell Counts in Cerebral Cortex of an Autistic Patient.

    Science.gov (United States)

    Coleman, Paul D.; And Others

    1985-01-01

    Numbers of neurons and glia were counted in the cerebral cortex of one case of autism and two age- and sex-matched controls. Cell counts were made in primary auditory cortex, Broca's speech area, and auditory association cortex. No consistent differences in cell density were found between brains of autistic and control patients. (Author/CL)

  3. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    Directory of Open Access Journals (Sweden)

    Francisco Bruno Teixeira

    Full Text Available Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies, GFAP (a marker of astrocytes and Iba1 (microglia marker in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  4. Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress

    OpenAIRE

    Francisco Bruno Teixeira; Luana Nazaré da Silva Santana; Fernando Romualdo Bezerra; Sabrina De Carvalho; Enéas Andrade Fontes-Júnior; Rui Daniel Prediger; Maria Elena Crespo-López; Cristiane Socorro Ferraz Maia; Rafael Rodrigues Lima

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, in...

  5. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  6. Laminar fate specification in the cerebral cortex

    Science.gov (United States)

    Gaspard, Nicolas

    2011-01-01

    The cerebral cortex is composed of hundreds of different types of neurons, which underlie its ability to perform highly complex neural processes. How this astonishing cell diversity is generated during development constitutes a major challenge in developmental neurosciences, with important implications for neurological diseases. Here we review some recent and exciting advances in this field, from the description of the cellular processes at the origin of cortical neuron diversity, to the dissection of the molecular logic underlying fate selection in cortical neurons. PMID:21655334

  7. Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex.

    Science.gov (United States)

    Ferreri, M C; Gutiérrez, M L; Gravielle, M C

    2015-12-03

    The clinical use of benzodiazepines is limited by the development of tolerance to their pharmacological effects. Tolerance to each of the pharmacological actions of benzodiazepines develops at different rates. The aim of this work was to investigate the mechanism of tolerance by performing behavioral tests in combination with biochemical studies. To this end, we administered prolonged treatments of diazepam to rats for 7 or 14 days. Tolerance to the sedative effects of diazepam was detected by means of the open field test after the 7- and 14-day treatments, whereas tolerance to the anxiolytic actions of benzodiazepine manifested following only the 14-day treatment in the elevated plus maze. The cerebral cortical concentrations of diazepam did not decline after the diazepam treatments, indicating that tolerance was not due to alterations in pharmacokinetic factors. The uncoupling of GABA/benzodiazepine site interactions and an increase in the degree of phosphorylation of the GABAA receptor γ2 subunit at serine 327 in the cerebral cortex were produced by day 7 of diazepam treatment and persisted after 14 days of exposure to benzodiazepine. Thus, these alterations could be part of the mechanism of tolerance to the sedative effects of diazepam. An increase in the percentage of α1-containing GABAA receptors in the cerebral cortex was observed following the 14-day treatment with diazepam but not the 7-day treatment, suggesting that tolerance to the anxiolytic effects is associated with a change in receptor subunit composition. The understanding of the molecular bases of tolerance could be important for the development of new drugs that maintain their efficacies over long-term treatments. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex.

    Science.gov (United States)

    Walker, Douglas G; Whetzel, Alexis M; Serrano, Geidy; Sue, Lucia I; Beach, Thomas G; Lue, Lih-Fen

    2015-02-01

    Recent findings identified the minor A allele present in the single-nucleotide polymorphism rs3865444 in the CD33 gene as being associated with the reduced risk of developing Alzheimer's disease (AD). CD33 (Siglec-3) is an immune function protein with anti-inflammatory signaling, cell adhesion, and endocytosis functions with sialic acid-modified proteins or lipids as ligands. Its involvement in AD pathologic mechanisms is still unclear; so, the goal of this study was to investigate if the rs3865444 polymorphism affects the development of AD pathology and the expression of CD33 messenger RNA (mRNA) and protein. For this study, we used DNA from 96 nondemented (ND) and 97 AD neuropathologically diagnosed cases to identify the different rs3865444 alleles and correlate with different measures of AD pathology. Using semiquantitative histologic measures of plaque and tangle pathology, we saw no significant differences between the different genotypes within these disease groups. However, increased expression of CD33 mRNA was associated with increasing AD pathology in temporal cortex brain samples. We also showed that cases with A/A alleles had reduced levels of CD33 protein in temporal cortex but increased levels of the microglia protein IBA-1. Using immunohistochemistry on temporal cortex sections, CD33 was selectively localized to microglia, with greater expression in activated microglia. The factors causing increased CD33 expression by microglia in brain are still unclear, although both genetic and disease factors are involved. Treatment of human microglia isolated from autopsy brains with amyloid-beta peptide and a range of other inflammatory activating agents resulted in reduced CD33 mRNA and protein levels. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls.

    Science.gov (United States)

    Lange, E H; Nerland, S; Jørgensen, K N; Mørch-Johnsen, L; Nesvåg, R; Hartberg, C B; Haukvik, U K; Osnes, K; Melle, I; Andreassen, O A; Agartz, I

    2017-03-01

    Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association. 1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes. Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity. The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.

  10. Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence.

    Science.gov (United States)

    Lenroot, Rhoshel K; Schmitt, James E; Ordaz, Sarah J; Wallace, Gregory L; Neale, Michael C; Lerch, Jason P; Kendler, Kenneth S; Evans, Alan C; Giedd, Jay N

    2009-01-01

    In this report, we present the first regional quantitative analysis of age-related differences in the heritability of cortical thickness using anatomic MRI with a large pediatric sample of twins, twin siblings, and singletons (n = 600, mean age 11.1 years, range 5-19). Regions of primary sensory and motor cortex, which develop earlier, both phylogenetically and ontologically, show relatively greater genetic effects earlier in childhood. Later developing regions within the dorsal prefrontal cortex and temporal lobes conversely show increasingly prominent genetic effects with maturation. The observation that regions associated with complex cognitive processes such as language, tool use, and executive function are more heritable in adolescents than children is consistent with previous studies showing that IQ becomes increasingly heritable with maturity(Plomin et al. 1997: Psychol Sci 8:442-447). These results suggest that both the specific cortical region and the age of the population should be taken into account when using cortical thickness as an intermediate phenotype to link genes, environment, and behavior. (c) 2007 Wiley-Liss, Inc.

  11. Comparative analyses of adeno-associated viral vector serotypes 1, 2, 5, 8 and 9 in marmoset, mouse and macaque cerebral cortex.

    Science.gov (United States)

    Watakabe, Akiya; Ohtsuka, Masanari; Kinoshita, Masaharu; Takaji, Masafumi; Isa, Kaoru; Mizukami, Hiroaki; Ozawa, Keiya; Isa, Tadashi; Yamamori, Tetsuo

    2015-04-01

    Here we investigated the transduction characteristics of adeno-associated viral vector (AAV) serotypes 1, 2, 5, 8 and 9 in the marmoset cerebral cortex. Using three constructs that each has hrGFP under ubiquitous (CMV), or neuron-specific (CaMKII and Synapsin I (SynI)) promoters, we investigated (1) the extent of viral spread, (2) cell type tropism, and (3) neuronal transduction efficiency of each serotype. AAV2 was clearly distinct from other serotypes in small spreading and neuronal tropism. We did not observe significant differences in viral spread among other serotypes. Regarding the cell tropism, AAV1, 5, 8 and 9 exhibited mostly glial expression for CMV construct. However, when the CaMKII construct was tested, cortical neurons were efficiently transduced (>∼70% in layer 3) by all serotypes, suggesting that glial expression obscured neuronal expression for CMV construct. For both SynI and CaMKII constructs, we observed generally high-level expression in large pyramidal cells especially in layer 5, as well as in parvalbumin-positive interneurons. The expression from the CaMKII construct was more uniformly observed in excitatory cells compared with SynI construct. Injection of the same viral preparations in mouse and macaque cortex resulted in essentially the same result with some species-specific differences. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. Functional involvement of cerebral cortex in human narcolepsy.

    Science.gov (United States)

    Oliviero, A; Della Marca, G; Tonali, P A; Pilato, F; Saturno, E; Dileone, M; Versace, V; Mennuni, G; Di Lazzaro, V

    2005-01-01

    The pathophysiology of human narcolepsy is still poorly understood. The hypoactivity of some neurotransmitter systems has been hypothesised on the basis of the canine model. To determine whether narcolepsy is associated with changes in excitability of the cerebral cortex, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in 13 patients with narcolepsy and in 12 control subjects. We used several TMS paradigms that can provide information on the excitability of the motor cortex. Resting and active motor thresholds were higher in narcoleptic patients than in controls and intracortical inhibition was more pronounced in narcoleptic patients. No changes in the other evaluated measures were detected. These results are consistent with an impaired balance between excitatory and inhibitory intracortical circuits in narcolepsy that leads to cortical hypoexcitability. We hypothesise that the deficiency of the excitatory hypocretin/orexin-neurotransmitter-system in narcolepsy is reflected in changes of cortical excitability since circuits originating in the lateral hypothalamus and in the basal forebrain project widely to the neocortex, including motor cortex. This abnormal excitability of cortical networks could be the physiological correlate of excessive daytime sleepiness and it could be the substrate for allowing dissociated states of wakefulness and sleep to emerge suddenly while patients are awake, which constitute the symptoms of narcolepsy.

  13. Genetic influences on thinning of the cerebral cortex during development

    NARCIS (Netherlands)

    van Soelen, I.L.C.; Brouwer, R.M.; van Baal, G.C.M.; Schnack, H.G.; Peper, J.S.; Collins, D.L.; Evans, A.C.; Kahn, R.S.; Boomsma, D.I.; Hulshoff Pol, H.E.

    2012-01-01

    During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain

  14. Glutamate Levels and Resting Cerebral Blood Flow in Anterior Cingulate Cortex Are Associated at Rest and Immediately Following Infusion of S-Ketamine in Healthy Volunteers

    OpenAIRE

    Kirsten Borup Bojesen; Kirsten Borup Bojesen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Lone Baandrup; Line Malmer Madsen; Birte Yding Glenthøj; Birte Yding Glenthøj; Egill Rostrup; Brian Villumsen Broberg

    2018-01-01

    Progressive loss of brain tissue is seen in some patients with schizophrenia and might be caused by increased levels of glutamate and resting cerebral blood flow (rCBF) alterations. Animal studies suggest that the normalisation of glutamate levels decreases rCBF and prevents structural changes in hippocampus. However, the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of humans has not been studied in the absence of antipsychotics and illness chronicity. Ketamine i...

  15. Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex.

    Science.gov (United States)

    Scremin, O U; Li, M G; Scremin, A M; Jenden, D J

    1997-01-01

    The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral cortex. The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.

  16. Hypoperfusion of cerebral cortex in renal hypertensive rats.

    Science.gov (United States)

    Wall, K M; Gross, P M

    1991-05-01

    Morphometric and physiological measurements in the parietal cortex of rats with 2-kidney-1-clip renal hypertension and their normotensive controls indicated a 23% increase in capillary bed volume accompanied by a 32% reduction in the rate of cortical blood flow in the renal hypertensive animals. From these measures, we estimated an 83% increase in the duration of blood transit through the cortical capillary network of renal hypertensive rats, a new expression of altered microvascular function in the brain of this hypertensive model. The rate of glucose utilization in the cerebral cortex of renal hypertensive animals was not different from that observed for normotensive animals. Thus, for capillary networks in cerebral cortex of renal hypertensive rats, we demonstrated markedly reduced rates of perfusion independent of tissue metabolic factors, despite expansion of capillary bed volume.

  17. Microglia in the Cerebral Cortex in Autism

    Science.gov (United States)

    Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

    2012-01-01

    We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

  18. High membrane protein oxidation in the human cerebral cortex.

    Science.gov (United States)

    Granold, Matthias; Moosmann, Bernd; Staib-Lasarzik, Irina; Arendt, Thomas; Del Rey, Adriana; Engelhard, Kristin; Behl, Christian; Hajieva, Parvana

    2015-01-01

    Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old animals, and adult rat hippocampus and cortex subjected or not subjected to cerebral ischemia. Most tissues showed relatively similar levels of protein oxidation. However, human cortex was affected by severe membrane protein oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In contrast, ex vivo autooxidation of murine cortical tissue primarily induced aqueous protein oxidation, while in vivo biological aging or cerebral ischemia had no major effect on brain protein oxidation. The unusually high levels of membrane protein oxidation in the human cortex were also not predicted by lipid peroxidation, as the levels of isoprostane immunoreactivity in human samples were considerably lower than in rodent tissues. Our results indicate that the aged human cortex is under steady pressure from specific and potentially detrimental membrane protein oxidation. The pronounced difference between humans, mice and rats regarding the primary site of cortical oxidation might have contributed to the unresolved difficulties in translating into therapies the wealth of data describing successful antioxidant neuroprotection in rodents. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. High membrane protein oxidation in the human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Matthias Granold

    2015-04-01

    Full Text Available Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old animals, and adult rat hippocampus and cortex subjected or not subjected to cerebral ischemia. Most tissues showed relatively similar levels of protein oxidation. However, human cortex was affected by severe membrane protein oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In contrast, ex vivo autooxidation of murine cortical tissue primarily induced aqueous protein oxidation, while in vivo biological aging or cerebral ischemia had no major effect on brain protein oxidation. The unusually high levels of membrane protein oxidation in the human cortex were also not predicted by lipid peroxidation, as the levels of isoprostane immunoreactivity in human samples were considerably lower than in rodent tissues. Our results indicate that the aged human cortex is under steady pressure from specific and potentially detrimental membrane protein oxidation. The pronounced difference between humans, mice and rats regarding the primary site of cortical oxidation might have contributed to the unresolved difficulties in translating into therapies the wealth of data describing successful antioxidant neuroprotection in rodents.

  20. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    Science.gov (United States)

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle.

  1. Neural substrate of dynamic Bayesian inference in the cerebral cortex.

    Science.gov (United States)

    Funamizu, Akihiro; Kuhn, Bernd; Doya, Kenji

    2016-12-01

    Dynamic Bayesian inference allows a system to infer the environmental state under conditions of limited sensory observation. Using a goal-reaching task, we found that posterior parietal cortex (PPC) and adjacent posteromedial cortex (PM) implemented the two fundamental features of dynamic Bayesian inference: prediction of hidden states using an internal state transition model and updating the prediction with new sensory evidence. We optically imaged the activity of neurons in mouse PPC and PM layers 2, 3 and 5 in an acoustic virtual-reality system. As mice approached a reward site, anticipatory licking increased even when sound cues were intermittently presented; this was disturbed by PPC silencing. Probabilistic population decoding revealed that neurons in PPC and PM represented goal distances during sound omission (prediction), particularly in PPC layers 3 and 5, and prediction improved with the observation of cue sounds (updating). Our results illustrate how cerebral cortex realizes mental simulation using an action-dependent dynamic model.

  2. [A case of progressive multifocal leukoencephalopathy presenting white matter MRI lesions extending over the cerebral cortex and a marked decrease in cerebral blood flow on SPECT, and associated with HTLV-I infection].

    Science.gov (United States)

    Takase, Kei-ichiro; Ohyagi, Yasumasa; Furuya, Hirokazu; Nagashima, Kazuo; Taniwaki, Takayuki; Kira, Jun-ichi

    2005-06-01

    We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein

  3. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Science.gov (United States)

    Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

    2013-01-01

    How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later

  4. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Directory of Open Access Journals (Sweden)

    Suzana eHerculano-Houzel

    2013-10-01

    Full Text Available How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005 to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes – with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (see companion paper and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity

  5. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  6. Convection-enhanced delivery of AAV2 in white matter--a novel method for gene delivery to cerebral cortex.

    Science.gov (United States)

    Barua, N U; Woolley, M; Bienemann, A S; Johnson, D; Wyatt, M J; Irving, C; Lewis, O; Castrique, E; Gill, S S

    2013-10-30

    Convection-enhanced delivery (CED) is currently under investigation for delivering therapeutic agents to subcortical targets in the brain. Direct delivery of therapies to the cerebral cortex, however, remains a significant challenge. We describe a novel method of targeting adeno-associated viral vector (AAV) mediated gene therapies to specific cerebral cortical regions by performing high volume, high flow rate infusions into underlying white matter in a large animal (porcine) model. Infusion volumes of up to 700 μl at flow rates as high as 10 μl/min were successfully performed in white matter without adverse neurological sequelae. Co-infusion of AAV2/5-GFP with 0.2% Gadolinium in artificial CSF confirmed transgene expression in the deep layers of cerebral cortex overlying the infused areas of white matter. AAV-mediated gene therapies have been previously targeted to the cerebral cortex by performing intrathalamic CED and exploiting axonal transport. The novel method described in this study facilitates delivery of gene therapies to specific regions of the cerebral cortex without targeting deep brain structures. AAV-mediated gene therapies can be targeted to specific cortical regions by performing CED into underlying white matter. This technique could be applied to the treatment of neurological disorders characterised by cerebral cortical degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. The response of cerebral cortex to haemorrhagic damage: experimental evidence from a penetrating injury model.

    Directory of Open Access Journals (Sweden)

    Sivaraman Purushothuman

    Full Text Available Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer's disease. In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3-5 months. Brains were examined after 1-30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP, for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer's disease was examined with the same techniques. Needlestick injury induced long-lasting changes-haem deposition, cell death, plaque-like deposits and glial invasion-along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the

  8. Tangential migration of neurons in the developing cerebral cortex.

    Science.gov (United States)

    O'Rourke, N A; Sullivan, D P; Kaznowski, C E; Jacobs, A A; McConnell, S K

    1995-07-01

    The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299-302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434-440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal

  9. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

    Science.gov (United States)

    Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

    2014-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

  10. Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans

    NARCIS (Netherlands)

    Williams, D; Tijssen, M; van Bruggen, G; Bosch, A; Insola, A; Di Lazzaro, V; Mazzone, P; Oliviero, A; Quartarone, A; Speelman, H; Brown, P

    2002-01-01

    We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from

  11. Early developmental actions of endocrine disruptors on the hypothalamus, hippocampus, and cerebral cortex.

    OpenAIRE

    Parent, Anne-Simone; NAVEAU, Elise; Gerard, Arlette; Bourguignon, Jean-Pierre; Gary L Westbrook

    2011-01-01

    Sex steroids and thyroid hormones play a key role in the development of the central nervous system. The critical role of these hormonal systems may explain the sensitivity of the hypothalamus, the cerebral cortex, and the hippocampus to endocrine-disrupting chemicals (EDC). This review examines the evidence for endocrine disruption of glial-neuronal functions in the hypothalamus, hippocampus, and cerebral cortex. Focus was placed on two well-studied EDC, the insecticide dichlorodiphenyltrichl...

  12. Radial Structure Scaffolds Convolution Patterns of Developing Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Mir Jalil Razavi

    2017-08-01

    Full Text Available Commonly-preserved radial convolution is a prominent characteristic of the mammalian cerebral cortex. Endeavors from multiple disciplines have been devoted for decades to explore the causes for this enigmatic structure. However, the underlying mechanisms that lead to consistent cortical convolution patterns still remain poorly understood. In this work, inspired by prior studies, we propose and evaluate a plausible theory that radial convolution during the early development of the brain is sculptured by radial structures consisting of radial glial cells (RGCs and maturing axons. Specifically, the regionally heterogeneous development and distribution of RGCs controlled by Trnp1 regulate the convex and concave convolution patterns (gyri and sulci in the radial direction, while the interplay of RGCs' effects on convolution and axons regulates the convex (gyral convolution patterns. This theory is assessed by observations and measurements in literature from multiple disciplines such as neurobiology, genetics, biomechanics, etc., at multiple scales to date. Particularly, this theory is further validated by multimodal imaging data analysis and computational simulations in this study. We offer a versatile and descriptive study model that can provide reasonable explanations of observations, experiments, and simulations of the characteristic mammalian cortical folding.

  13. Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

    Science.gov (United States)

    Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

    2011-01-01

    Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

  14. Epidemiologic associations with cerebral palsy.

    Science.gov (United States)

    O'Callaghan, Michael E; MacLennan, Alastair H; Gibson, Catherine S; McMichael, Gai L; Haan, Eric A; Broadbent, Jessica L; Goldwater, Paul N; Dekker, Gustaaf A

    2011-09-01

    To estimate epidemiologic risk factors for cerebral palsy. Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non-cerebral palsy controls. The following factors were associated with cerebral palsy: recorded maternal infection during pregnancy (41.4% patients compared with 31.3% controls; odds ratio [OR] 1.55, 95% confidence interval 1.26-1.91), small for gestational age ([birth weight less than third customized centile] 43.9% patients compared with 6.3% controls; OR 11.75, 6.25-22.08), gestational age less than 32 weeks (29.3% patients compared with 0.7% controls; OR 59.20, 28.87-121.38), multiple birth (OR 6.62, 4.00-10.95), a relative with cerebral palsy (OR 1.61, 1.12-2.32), breech position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76-3.49), bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls; OR 2.04, 1.61-2.58), male sex (58.8% patients compared with 45.8% controls; OR 1.68, 1.38-2.06), multiple miscarriage (7.7% patients compared with 3.5% controls; OR 2.30, 1.38-3.82), smoking (14.0% patients compared with 10.6% controls; OR 1.37, 1.02-1.85), and illicit drug use (3.3% patients compared with 1.5% controls; OR 2.22, 1.14-4.30). Factors not associated with cerebral palsy were "disappearing twin," diabetes, maternal body mass index, hypertension, alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery, and maternal age. Preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth present the largest risks for a cerebral palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal infections during pregnancy were not associated with cerebral palsy. II.

  15. Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar; Burkeen, Jeffrey; Connor, Michael [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Krishnan, Anitha Priya; White, Nathan S.; Farid, Nikdokht; Bartsch, Hauke [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Murzin, Vyacheslav [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Nguyen, Tanya T. [Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Brewer, James B. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Dale, Anders M. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)

    2017-04-01

    Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations

  16. Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes.

    Science.gov (United States)

    Lin, Tzu-Yu; Chung, Chih-Yang; Lu, Cheng-Wei; Huang, Shu-Kuei; Shieh, Jiann-Sing; Wang, Su-Jane

    2013-09-01

    Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low-dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose-dependent inhibition of 4-AP-evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization-induced increase in [Ca²⁺]C but did not alter 4-AP-mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]C caused by Ca²⁺ entry through presynaptic voltage-dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades. Copyright © 2013 Wiley Periodicals, Inc.

  17. Microvasculature of the Mouse Cerebral Cortex Exhibits Increased Accumulation and Synthesis of Hyaluronan With Aging.

    Science.gov (United States)

    Reed, May J; Vernon, Robert B; Damodarasamy, Mamatha; Chan, Christina K; Wight, Thomas N; Bentov, Itay; Banks, William A

    2017-06-01

    The microvasculature of the aged brain is less dense and more vulnerable to dysfunction than that of the young brain. Brain microvasculature is supported by its surrounding extracellular matrix, which is comprised largely of hyaluronan (HA). HA is continually degraded into lower molecular weight forms that induce neuroinflammation. We examined HA associated with microvessels (MV) of the cerebral cortex of young (4 months), middle-aged (14 months), and aged (24-26 months) mice. We confirmed that the density of cortical MV decreased with age. Perivascular HA levels increased with age, but there was no age-associated change in HA molecular weight profile. MV isolated from aged cortex had more HA than MV from young cortex. Examination of mechanisms that might account for elevated HA levels with aging showed increased HA synthase 2 (HAS2) mRNA and protein in aged MV relative to young MV. In contrast, mRNAs for HA-degrading hyaluronidases or hyaladherins that mitigate HA degradation showed no changes with age. Corresponding to increased HAS2, aged MV synthesized significantly more HA (of all molecular weight classes) in vitro than young MV. We propose that increased HA synthesis and accumulation in brain MV contributes to neuroinflammation and reduced MV density and function in aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Reproducibility of T2 * mapping in the human cerebral cortex in vivo at 7 tesla MRI.

    Science.gov (United States)

    Govindarajan, Sindhuja T; Cohen-Adad, Julien; Sormani, Maria Pia; Fan, Audrey P; Louapre, Céline; Mainero, Caterina

    2015-08-01

    To assess the test-retest reproducibility of cortical mapping of T2 * relaxation rates at 7 Tesla (T) MRI. T2 * maps have been used for studying cortical myelo-architecture patterns in vivo and for characterizing conditions associated with changes in iron and/or myelin concentration. T2 * maps were calculated from 7T multi-echo T2 *-weighted images acquired during separate scanning sessions on 8 healthy subjects. The reproducibility of surface-based cortical T2 * mapping was assessed at different depths of the cortex; from pial surface (0% depth) towards gray/white matter boundary (100% depth), across cortical regions and hemispheres, using coefficients of variation (COVs = SD/mean) between each couple (scan-rescan) of average T2 * measurements. Average cortical T2 * was significantly different among 25%, 50%, and 75% depths (analysis of variance, P < 0.001). Coefficient of variations were very low within cortical regions, and whole cortex (average COV = 0.83-1.79%), indicating a high degree of reproducibility in T2 * measures. Surface-based mapping of T2 * relaxation rates as a function of cortical depth is reproducible and could prove useful for studying the laminar architecture of the cerebral cortex in vivo, and for investigating physiological and pathological states associated with changes in iron and/or myelin concentration. © 2014 Wiley Periodicals, Inc.

  19. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.

    Directory of Open Access Journals (Sweden)

    Nelle Lambert

    2011-03-01

    Full Text Available The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits.

  20. Spatiotemporal Organization and Cross-Frequency Coupling of Sleep Spindles in Primate Cerebral Cortex

    Science.gov (United States)

    Takeuchi, Saori; Murai, Rie; Shimazu, Hideki; Isomura, Yoshikazu; Mima, Tatsuya; Tsujimoto, Toru

    2016-01-01

    Study Objectives: The sleep spindle has been implicated in thalamic sensory gating, cortical development, and memory consolidation. These multiple functions may depend on specific spatiotemporal emergence and interactions with other spindles and other forms of brain activity. Therefore, we measured sleep spindle cortical distribution, regional heterogeneity, synchronization, and phase relationships with other electroencephalographic components in freely moving primates. Methods: Transcortical field potentials were recorded from Japanese monkeys via telemetry and were analyzed using the Hilbert-Huang transform. Results: Spindle (12–20 Hz) current sources were identified over a wide region of the frontoparietal cortex. Most spindles occurred independently in their own frequency, but some appeared concordant between cortical areas with frequency interdependence, particularly in nearby regions and bilaterally symmetrical regions. Spindles in the dorsolateral prefrontal cortex appeared around the surface-positive and depth-negative phase of transcortically recorded slow oscillations (generators, but are temporally associated to spindles in other regions and to slow and gamma oscillations by corticocortical and thalamocortical pathways. Citation: Takeuchi S, Murai R, Shimazu H, Isomura Y, Mima T, Tsujimoto T. Spatiotemporal organization and cross-frequency coupling of sleep spindles in primate cerebral cortex. SLEEP 2016;39(9):1719–1735. PMID:27397568

  1. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Juan P. Hernández-Fonseca

    2009-01-01

    Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

  2. Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex.

    Science.gov (United States)

    Silver, Debra L

    2016-02-01

    The cerebral cortex controls our most distinguishing higher cognitive functions. Human-specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non-coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and organoids, offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits. © 2015 WILEY Periodicals, Inc.

  3. Genetic and Molecular Approaches to Study Neuronal Migration in the Developing Cerebral Cortex.

    Science.gov (United States)

    Dudok, Jacobus J; Leonards, Pim E G; Wijnholds, Jan

    2017-05-05

    The migration of neuronal cells in the developing cerebral cortex is essential for proper development of the brain and brain networks. Disturbances in this process, due to genetic abnormalities or exogenous factors, leads to aberrant brain formation, brain network formation, and brain function. In the last decade, there has been extensive research in the field of neuronal migration. In this review, we describe different methods and approaches to assess and study neuronal migration in the developing cerebral cortex. First, we discuss several genetic methods, techniques and genetic models that have been used to study neuronal migration in the developing cortex. Second, we describe several molecular approaches to study aberrant neuronal migration in the cortex which can be used to elucidate the underlying mechanisms of neuronal migration. Finally, we describe model systems to investigate and assess the potential toxicity effect of prenatal exposure to environmental chemicals on proper brain formation and neuronal migration.

  4. Preliminary study on sarcoglycan sub-complex in rat cerebral and cerebellar cortex.

    Science.gov (United States)

    Vermiglio, Giovanna; Runci, Michele; Scibilia, Antonino; Biasini, Fiammetta; Cutroneo, Giuseppina

    2012-01-01

    The sarcoglycan sub-complex is a protein system which plays a key role in sarcolemma stabilization during muscle activity. Although numerous studies have been conducted on this system, there are few data about its localization in non-muscular tissues. On this basis we carried out an indirect immunofluorescence study on normal rat cerebral and cerebellar cortex. In particular, we carried out single localization reactions to analyze if these proteins are present in brain and double localization reactions between sarcoglycans and either SMI-32 or GFAP to verify if they are expressed both in neurons and glial cells. We found that all tested sarcoglycans are present both in cerebral and cerebellar cortex and that they are expressed both in neurons and glial cells. The typical staining pattern of all sarcoglycans is represented by "spot-like" fluorescence, with spots of 0.5-2 microm average diameter laid out mainly around the soma of the cells. The main difference about sarcoglycans expression between cerebral and cerebellar cortex is that in the cerebellar cortex the sarcoglycans positivity is detectable only in an area which is likely to correspond to Purkinje cells layer. The presence of sarcoglycans in cerebral and cerebellar cortex and their disposition mainly around the soma of the cells suggest a role of these proteins in cellular signalling and in regulating postsynaptic receptor assembly mainly in axo-somatic synapses.

  5. High membrane protein oxidation in the human cerebral cortex

    OpenAIRE

    Granold, Matthias; Moosmann, Bernd; Staib-Lasarzik, Irina; Arendt, Thomas; del Rey, Adriana; Engelhard, Kristin; Behl, Christian; Hajieva, Parvana

    2014-01-01

    Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old anim...

  6. CRYOPRESERVATION OF FRESHLY ISOLATED SYNAPTOSOMES PREPARED FROM THE CEREBRAL-CORTEX OF RATS

    NARCIS (Netherlands)

    GLEITZ, J; BEILE, A; WILFFERT, B; TEGTMEIER, F

    In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group

  7. Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

    African Journals Online (AJOL)

    Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

  8. An automated pipeline for cortical surface generation and registration of the cerebral cortex

    Science.gov (United States)

    Li, Wen; Ibanez, Luis; Gelas, Arnaud; Yeo, B. T. Thomas; Niethammer, Marc; Andreasen, Nancy C.; Magnotta, Vincent A.

    2011-03-01

    The human cerebral cortex is one of the most complicated structures in the body. It has a highly convoluted structure with much of the cortical sheet buried in sulci. Based on cytoarchitectural and functional imaging studies, it is possible to segment the cerebral cortex into several subregions. While it is only possible to differentiate the true anatomical subregions based on cytoarchitecture, the surface morphometry aligns closely with the underlying cytoarchitecture and provides features that allow the surface of the cortex to be parcellated based on the sulcal and gyral patterns that are readily visible on the MR images. We have developed a fully automated pipeline for the generation and registration of cortical surfaces in the spherical domain. The pipeline initiates with the BRAINS AutoWorkup pipeline. Subsequently, topology correction and surface generation is performed to generate a genus zero surface and mapped to a sphere. Several surface features are then calculated to drive the registration between the atlas surface and other datasets. A spherical diffeomorphic demons algorithm is used to co-register an atlas surface onto a subject surface. A lobar based atlas of the cerebral cortex was created from a manual parcellation of the cortex. The atlas surface was then co-registered to five additional subjects using a spherical diffeomorphic demons algorithm. The labels from the atlas surface were warped on the subject surface and compared to the manual raters. The average Dice overlap index was 0.89 across all regions.

  9. Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism

    Directory of Open Access Journals (Sweden)

    Turner Katherine C

    2006-10-01

    Full Text Available Abstract Background Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. Methods Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI effects were identified as interregional blood oxygenation level dependent (BOLD signal cross-correlation, using the caudate nuclei as seed volumes. Results In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits. Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex. Conclusion These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

  10. [Expression of CaMK II delta in cerebral cortex following traumatic brain injury].

    Science.gov (United States)

    Pan, Hong; Zhang, Jing-Jing; Xu, Dong-Dong; Gu, Zhen-Yong; Tao, Lu-Yang; Zhang, Ming-Yang

    2014-06-01

    To observe the time-course expression of calcium-calmodulin dependent protein kinase II delta (CaMK II delta) in cerebral cortex after traumatic brain injury (TBI). The TBI rat model was established. The expression of CaMK II delta in cerebral cortex around injured area was tested by Western blotting and immunohistochemical staining. Western blotting revealed expression of CaMK II delta in normal rat brain cortex. It gradually increased after TBI, peaked after 3 days, and then returned to normal level. The result of immunohistochemical staining was consistent with that of Western blotting. The expression of CaMK II delta around injured area after TBI increased initially and then decreased. It could be used as a new indicator for wound age determination following TBI.

  11. Early developmental actions of endocrine disruptors on the hypothalamus, hippocampus, and cerebral cortex.

    Science.gov (United States)

    Parent, Anne-Simone; Naveau, Elise; Gerard, Arlette; Bourguignon, Jean-Pierre; Westbrook, Gary L

    2011-01-01

    Sex steroids and thyroid hormones play a key role in the development of the central nervous system. The critical role of these hormonal systems may explain the sensitivity of the hypothalamus, the cerebral cortex, and the hippocampus to endocrine-disrupting chemicals (EDC). This review examines the evidence for endocrine disruption of glial-neuronal functions in the hypothalamus, hippocampus, and cerebral cortex. Focus was placed on two well-studied EDC, the insecticide dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCB). DDT is involved in neuroendocrine disruption of the reproductive axis, whereas polychlorinated biphenyls (PCB) interact with both the thyroid hormone- and sex steroid-dependent systems and disturb the neuroendocrine control of reproduction and development of hippocampus and cortex. These results highlight the impact of EDC on the developing nervous system and the need for more research in this area.

  12. Sox11 Balances Dendritic Morphogenesis with Neuronal Migration in the Developing Cerebral Cortex.

    Science.gov (United States)

    Hoshiba, Yoshio; Toda, Tomohisa; Ebisu, Haruka; Wakimoto, Mayu; Yanagi, Shigeru; Kawasaki, Hiroshi

    2016-05-25

    The coordinated mechanisms balancing promotion and suppression of dendritic morphogenesis are crucial for the development of the cerebral cortex. Although previous studies have revealed important transcription factors that promote dendritic morphogenesis during development, those that suppress dendritic morphogenesis are still largely unknown. Here we found that the expression levels of the transcription factor Sox11 decreased dramatically during dendritic morphogenesis. Our loss- and gain-of-function studies using postnatal electroporation and in utero electroporation indicate that Sox11 is necessary and sufficient for inhibiting dendritic morphogenesis of excitatory neurons in the mouse cerebral cortex during development. Interestingly, we found that precocious suppression of Sox11 expression caused precocious branching of neurites and a neuronal migration defect. We also found that the end of radial migration induced the reduction of Sox11 expression. These findings indicate that suppression of dendritic morphogenesis by Sox11 during radial migration is crucial for the formation of the cerebral cortex. Because dendritic morphology has profound impacts on neuronal information processing, the mechanisms underlying dendritic morphogenesis during development are of great interest. Our loss- and gain-of-function studies indicate that Sox11 is necessary and sufficient for inhibiting dendritic morphogenesis of excitatory neurons in the mouse cerebral cortex during development. Interestingly, we found that precocious suppression of Sox11 expression caused a neuronal migration defect. These findings indicate that suppression of dendritic morphogenesis by Sox11 during radial migration is crucial for the formation of the cerebral cortex. Copyright © 2016 the authors 0270-6474/16/365775-10$15.00/0.

  13. Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning.

    Science.gov (United States)

    Exeli, Ann-Katrin; Kellner, Daniel; Exeli, Lukas; Steininger, Phil; Wolf, Frank; Sedlmayer, Felix; Deutschmann, Heinz

    2018-02-06

    To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients. Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing. Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 - 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 - 8%). We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing.

  14. Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

    Science.gov (United States)

    Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

    2016-08-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds.

  15. Cerebral Cortex Expression of Gli3 Is Required for Normal Development of the Lateral Olfactory Tract

    Science.gov (United States)

    Amaniti, Eleni-Maria; Kelman, Alexandra; Mason, John O.; Theil, Thomas

    2015-01-01

    Formation of the lateral olfactory tract (LOT) and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. Gli3 null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for Gli3 in its development. Here, we used Emx1Cre;Gli3fl/fl conditional mutants to investigate LOT formation and colonization of the olfactory cortex in embryos in which loss of Gli3 function is restricted to the dorsal telencephalon. These mutants form an olfactory bulb like structure which does not protrude from the telencephalic surface. Nevertheless, mitral cells are formed and their axons enter the piriform cortex though the LOT is shifted medially. Mitral axons also innervate a larger target area consistent with an enlargement of the piriform cortex and form aberrant projections into the deeper layers of the piriform cortex. No obvious differences were found in the expression patterns of key guidance cues. However, we found that an expansion of the piriform cortex temporally coincides with the arrival of LOT axons, suggesting that Gli3 affects LOT positioning and target area innervation through controlling the development of the piriform cortex. PMID:26509897

  16. Functional involvement of cerebral cortex in adult sleepwalking.

    Science.gov (United States)

    Oliviero, A; Della Marca, G; Tonali, P A; Pilato, F; Saturno, E; Dileone, M; Rubino, M; Di Lazzaro, V

    2007-08-01

    The pathophysiology of adult sleepwalking is still poorly understood. However, it is widely accepted that sleepwalking is a disorder of arousal. Arousal circuits widely project to the cortex, including motor cortex. We hypothesized that functional abnormality of these circuits could lead to changes in cortical excitability in sleepwalkers, even during wakefulness. We used transcranial magnetic stimulation (TMS) to examine the excitability of the human motor cortex during wakefulness in a group of adult sleepwalkers. When compared with the healthy control group, short interval intracortical inhibition (SICI), cortical silent period (CSP) duration, and short latency afferent inhibition (SAI) were reduced in adult sleepwalkers during wakefulness. Mean CSP duration was shorter in patients than in controls (80.9 +/- 41 ms vs. 139.4 +/- 37 ms; p = 0.0040). Mean SICI was significantly reduced in patients than in controls (73.5 +/- 38.4% vs. 36.7 +/- 13.1%; p = 0.0061). Mean SAI was also significantly reduced in patients than in controls (65.8 +/- 14.2% vs. 42.8 +/- 16.9%; p = 0.0053). This neurophysiological study suggests that there are alterations in sleepwalkers consistent with an impaired efficiency of inhibitory circuits during wakefulness. This inhibitory impairment could represent the neurophysiological correlate of brain "abnormalities" of sleepwalkers like "immaturity" of some neural circuits, synapses, or receptors.

  17. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

    Directory of Open Access Journals (Sweden)

    Bárbara Núñez

    Full Text Available Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2 cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8, in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

  18. Characterization of primary and secondary cultures of astrocytes prepared from mouse cerebral cortex

    DEFF Research Database (Denmark)

    Skytt, Dorte Marie; Madsen, Karsten Kirkegaard; Pajecka, Kamilla

    2010-01-01

    Astrocyte cultures were prepared from cerebral cortex of new-born and 7-day-old mice and additionally, the cultures from new-born animals were passaged as secondary cultures. The cultures were characterized by immunostaining for the astrocyte markers glutamine synthetase (GS), glial fibrillary...... of the astrocyte marker proteins. The metabolic pattern of the cultures from 7-day-old animals of the labeled substrates was comparable to that seen previously in astrocyte cultures prepared from new-born mouse brain showing pronounced glycolytic and oxidative metabolism of glucose. Glutamate was metabolized both...... cerebral cortex of 7-day-old mice have metabolic and functional properties indistinguishable from those of classical astrocyte cultures prepared from neocortex of new-born animals. This provides flexibility with regard to preparation and use of these cultures for a variety of purposes....

  19. Immunohistochemical investigation of neuronal injury in cerebral cortex of cobra-envenomed rats

    OpenAIRE

    RAHMY, T. R.; Hassona, I.A.

    2004-01-01

    The immunohistochemical expression of neuron-specific enolase, NSE (a cytoplasmic glycolytic enzyme of the neurons), synaptophysin, SYN (a major membrane glycoprotein of synaptic vesicles), and Bcl-2 (anti-apoptotic protein) were determined in cerebral cortex of rats envenomed with neurotoxic venom from Egyptian cobra. Male rats were intramuscularly (IM) injected with a single injection of either physiological saline solution or ½ LD50 or LD50 of cobra venom and sacrificed 24, 48, or 72 hr af...

  20. Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

    OpenAIRE

    Acaz-Fonseca, Estefan?a; Ortiz-Rodriguez, Ana; Lopez-Rodriguez, Ana B.; Garcia-Segura, Luis M.; Astiz, Mariana

    2017-01-01

    Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In male...

  1. Immunohistochemical investigation of neuronal injury in cerebral cortex of cobra-envenomed rats

    Directory of Open Access Journals (Sweden)

    T.R. Rahmy

    2004-01-01

    Full Text Available The immunohistochemical expression of neuron-specific enolase, NSE (a cytoplasmic glycolytic enzyme of the neurons, synaptophysin, SYN (a major membrane glycoprotein of synaptic vesicles, and Bcl-2 (anti-apoptotic protein were determined in cerebral cortex of rats envenomed with neurotoxic venom from Egyptian cobra. Male rats were intramuscularly (IM injected with a single injection of either physiological saline solution or ½ LD50 or LD50 of cobra venom and sacrificed 24, 48, or 72 hr after envenoming. Formalin-fixed paraffin sections were immunohistochemically studied by avidin-biotin-peroxidase complex method. Neuron histological structure and isolation of genomic DNA were also detected. The results showed a dose and time-dependent increase in NSE and SYN immunoreactivity in cerebral cortex of envenomed rats except in 72 hr high dose envenoming, where decreased SYN was observed. On the other hand, low dose venom induced high Bcl-2 expression 24 hr after envenoming, while the high dose decreased Bcl-2 protein expression. Temporal and spatial Bcl-2 expression was accompanied by DNA fragmentation in cerebral cortex of all envenomed rats, although no serious histological alterations were noticed. These results suggest that cobra venom may lead to neuronal injury and impairment of axonal transport as ascertained by alterations in NSE and SYN immunoreactivity. It could also indicate that venom alters the molecular machinery of apoptosis by inhibiting Bcl-2 expression; however, some vulnerable cells have the ability to overcome this by increasing Bcl-2 protein. These immunohistochemical investigations can be used as tools for detecting neuronal abnormalities even before the occurrence of any histological alterations in case of cerebral cortex neurotoxicity.

  2. Histopathologic Effect of Prenatal Topiramate Exposure on Rat Cerebral Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Hagar A Hashish

    2014-04-01

    Material and methods: 12 female pregnant rats were divided into control and treated groups, 6 rats in each group. The treated group was given topiramate dissolved in tap water, from day 0 of pregnancy till the delivery, through oral route in dose of 200mg/kg. The control group received tap water at the same time. In the end of the treatment, the cerebral cortex and the hippocampus were stained with hematoxylin and eosin (H and E and immnunohistochemically for glial fibrillary acidic protein (GFAP. Results: The control rat cerebral cortex showed that granule cells were small cell with dense cytoplasm, pyramidal cells appeared with triangular cell body, light cytoplasm and small nucleus. Strong GFAP positive immunostaining was detected in the astrocytes in both granule cell and pyramidal cell layers. The pyramidal cells in Cornu Ammonis showed characteristic palisade arrangement, with lightly stained cytoplasm and central nucleus. Granule cells of the dentate gyrus were rounded, packed, dense. Strong GFAP positive immunostaining was detected in the astrocytes in both pyramidal cell and granule cell layers. In treated rats, granule and pyramidal cells in the cerebral cortex and hippocampus were disorganized with signs of degeneration. Faint GFAP positive immunostaining was detected in the astrocytes in granule and pyramidal cell layers. Conclusion: Long-term daily use of topiramate during pregnancy can lead to noticeable pathological neurotoxic effect in the cerebral cortex and hippocampus which may be implicated in cognitive affection. Neurological effect of topiramate necessitates further investigations. [J Interdiscipl Histopathol 2014; 2(2.000: 61-68

  3. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

    Science.gov (United States)

    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

    2015-09-15

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

  4. The importance of video editing in automated image analysis in studies of the cerebral cortex.

    Science.gov (United States)

    Terry, R D; Deteresa, R

    1982-03-01

    Editing of the video image in computerized image analysis is readily accomplished with the appropriate apparatus, but slows the assay very significantly. In dealing with the cerebral cortex, however video editing is of considerable importance in that cells are very often contiguous to one another or are partially superimposed, and this gives an erroneous measurement unless those cells are artificially separated. Also important is elimination of vascular cells from consideration by the automated counting apparatus. A third available mode of editing allows the filling-in of the cytoplasm of cell bodies which are not fully stained with sufficient intensity to be wholly detected. This study, which utilizes 23 samples, demonstrates that, in a given area of a histologic section of cerebral cortex, the number of small cells is greater and the number of large neurons is smaller with editing than without. In that not all cases follow this general pattern, inadequate editing may lead to significant errors on individual specimens as well as to the calculated mean. Video editing is therefore an essential part of the morphometric study of cerebral cortex by means of automated image analysis.

  5. Cholinergic receptor alterations in the cerebral cortex of spinal cord injured rat

    Directory of Open Access Journals (Sweden)

    R. Chinthu

    2017-07-01

    Full Text Available Many areas of the cerebral cortex process sensory information or coordinate motor output necessary for control of movement. Disturbances in cortical cholinergic system can affect locomotor coordination. Spinal cord injury causes severe motor impairment and disturbances in cholinergic signalling can aggravate the situation. Considering the impact of cortical cholinergic firing in locomotion, we focussed the study in understanding the cholinergic alterations in cerebral cortex during spinal cord injury. The gene expression of key enzymes in cholinergic pathway - acetylcholine esterase and choline acetyl transferase showed significant upregulation in the cerebral cortex of spinal cord injured group compared to control with the fold increase in expression of acetylcholine esterase prominently higher than cholineacetyl transferase. The decreased muscarinic receptor density and reduced immunostaining of muscarinic receptor subtypes along with down regulated gene expression of muscarinic M1 and M3 receptor subtypes accounts for dysfunction of metabotropic acetylcholine receptors in spinal cord injury group. Ionotropic acetylcholine receptor alterations were evident from the decreased gene expression of alpha 7 nicotinic receptors and reduced immunostaining of alpha 7 nicotinic receptors in confocal imaging. Our data pin points the disturbances in cortical cholinergic function due to spinal cord injury; which can augment the locomotor deficits. This can be taken into account while devising a proper therapeutic approach to manage spinal cord injury.

  6. Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice.

    Science.gov (United States)

    Dono, R; Texido, G; Dussel, R; Ehmke, H; Zeller, R

    1998-08-03

    Fibroblast growth factor-2 (FGF-2) has been implicated in various signaling processes which control embryonic growth and differentiation, adult physiology and pathology. To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous recombination in mouse embryonic stem cells. FGF-2-deficient mice are viable, but display cerebral cortex defects at birth. Bromodeoxyuridine pulse labeling of embryos showed that proliferation of neuronal progenitors is normal, whereas a fraction of them fail to colonize their target layers in the cerebral cortex. A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are not limited to the cerebral cortex, as ectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord. Physiological studies showed that FGF-2-deficient adult mice are hypotensive. They respond normally to angiotensin II-induced hypertension, whereas neural regulation of blood pressure by the baroreceptor reflex is impaired. The present genetic study establishes that FGF-2 participates in controlling fates, migration and differentiation of neuronal cells, whereas it is not essential for their proliferation. The observed autonomic dysfunction in FGF-2-deficient adult mice uncovers more general roles in neural development and function.

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

    Science.gov (United States)

    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.

  8. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Functional evaluation of cerebral cortex in dementia with Lewy bodies.

    Science.gov (United States)

    Di Lazzaro, Vincenzo; Pilato, Fabio; Dileone, Michele; Saturno, Eleonora; Profice, Paolo; Marra, Camillo; Daniele, Antonio; Ranieri, Federico; Quaranta, Davide; Gainotti, Guido; Tonali, Pietro A

    2007-08-15

    Neurochemical investigations have demonstrated central cholinergic dysfunction in patients with dementia with Lewy bodies (DLB). Central cholinergic circuits of the human brain can be tested non-invasively by coupling peripheral nerve stimulation with transcranial magnetic stimulation of the contralateral motor cortex. This test, named short latency afferent inhibition has been shown in healthy subjects to be sensitive to the blockage of muscarinic acetylcholine receptors and it is impaired in patients with Alzheimer disease (AD), a cholinergic form of dementia, while it is normal in non-cholinergic forms of dementia such as fronto-temporal dementia. We evaluated short latency afferent inhibition in a group of patients with DLB and compared the data with that from a group of AD patients and a control group of age-matched healthy individuals. Short latency afferent inhibition was significantly reduced in DLB and AD patients. The findings suggest that this method can be used as a non-invasive test for the assessment of cholinergic pathways in patients with dementia and may represent a useful additional tool for discriminating between cholinergic and non-cholinergic forms of dementia.

  10. Myelin damage of hippocampus and cerebral cortex in rat pentylenetetrazol model.

    Science.gov (United States)

    You, Yu; Bai, Hui; Wang, Chao; Chen, Liang-Wei; Liu, Bei; Zhang, Hua; Gao, Guo-Dong

    2011-03-24

    Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures, which also occur in demyelinating diseases of the central nervous system (CNS) with a higher prevalence. Meanwhile, demyelination occurrings have been occasionally observed in CNS of epilepsy patients, indicating an association between demyelination and epileptic seizures by an unknown mechanism. However, no confirmative experimental evidence has yet been given. Thus, by using a rat pentylenetetrazol model, electroencephalogram (EEG), Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, the present study provided direct evidence that myelin sheath damage in rat hippocampus and cerebral cortex started in the early stage of epileptic seizures induction and lasted with no further increase in severity in the development of epileptic seizures. It was illustrated that myelin sheath damage was not the result of oligodendrocyte destruction, but the autoantibodies against myelin basic protein (MBP) produced in peripheral circulation accompanied by increased permeability of blood-brain barrier (BBB) formed in the development of epileptic seizures. This study firstly provided experimental evidence for myelin sheath damage in PTZ-induced rat's epileptic seizures and further demonstrated that its possible cause was autoimmunoreaction. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. PDT-induced epigenetic changes in the mouse cerebral cortex: a protein microarray study.

    Science.gov (United States)

    Demyanenko, S V; Uzdensky, A B; Sharifulina, S A; Lapteva, T O; Polyakova, L P

    2014-01-01

    Photodynamic therapy (PDT) is used for cancer treatment including brain tumors. But the role of epigenetic processes in photodynamic injury of normal brain tissue is unknown. 5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), was used to photosensitize mouse cerebral cortex. PpIX accumulation in cortical tissue was measured spectrofluorometrically. Hematoxylin/eosin, gallocyanin-chromalum and immunohistochemical staining were used to study morphological changes in PDT-treated cerebral cortex. Proteomic antibody microarrays were used to evaluate expression of 112 proteins involved in epigenetic regulation. ALA administration induced 2.5-fold increase in the PpIX accumulation in the mouse brain cortex compared to untreated mice. Histological study demonstrated PDT-induced injury of some neurons and cortical vessels. ALA-PDT induced dimethylation of histone H3, upregulation of histone deacetylases HDAC-1 and HDAC-11, and DNA methylation-dependent protein Kaiso that suppressed transcriptional activity. Upregulation of HDAC-1 and H3K9me2 was confirmed immunohistochemically. Down-regulation of transcription factor FOXC2, PABP, and hBrm/hsnf2a negatively regulated transcription. Overexpression of phosphorylated histone H2AX indicated activation of DNA repair, but down-regulation of MTA1/MTA1L1 and PML - impairment of DNA repair. Overexpression of arginine methyltransferase PRMT5 correlated with up-regulation of transcription factor E2F4 and importin α5/7. ALA-PDT injures and kills some but not all neurons and caused limited microvascular alterations in the mouse cerebral cortex. It alters expression of some proteins involved in epigenetic regulation of transcription, histone modification, DNA repair, nuclear protein import, and proliferation. These data indicate epigenetic markers of photo-oxidative injury of normal brain tissue. © 2013.

  12. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  13. Human Development XI: The Structure of the Cerebral Cortex. Are There Really Modules in the Brain?

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2007-01-01

    Full Text Available The structure of human consciousness is thought to be closely connected to the structure of cerebral cortex. One of the most appreciated concepts in this regard is the Szanthagothei model of a modular building of neo-cortex. The modules are believed to organize brain activity pretty much like a computer. We looked at examples in the literature and argue that there is no significant evidence that supports Szanthagothei's model. We discuss the use of the limited genetic information, the corticocortical afferents termination and the columns in primary sensory cortex as arguments for the existence of the cortex-module. Further, we discuss the results of experiments with Luminization Microscopy (LM colouration of myalinized fibres, in which vertical bundles of afferent/efferent fibres that could support the cortex module are identified. We conclude that sensory maps seem not to be an expression for simple specific connectivity, but rather to be functional defined. We also conclude that evidence for the existence of the postulated module or column does not exist in the discussed material. This opens up for an important discussion of the brain as functionally directed by biological information (information-directed self-organisation, and for consciousness being closely linked to the structure of the universe at large. Consciousness is thus not a local phenomena limited to the brain, but a much more global phenomena connected to the wholeness of the world.

  14. Are you also what your mother eats? Distinct proteomic portrait as a result of maternal high-fat diet in the cerebral cortex of the adult mouse.

    Science.gov (United States)

    Manousopoulou, A; Woo, J; Woelk, C H; Johnston, H E; Singhania, A; Hawkes, C; Garbis, S D; Carare, R O

    2015-08-01

    Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Our aim was to compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Male mice born to dams fed a control (C) or high-fat (H) diet 4 weeks before conception and during gestation, and lactation were assigned to either C or H diet at weaning. Mice were killed at 19 weeks and their cerebral cortices were analysed using a two-dimensional liquid chromatography-mass spectrometry methodology. In total, 6 695 proteins were identified (qdiet of the mother and not their own diet and that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Maternal high-fat diet resulted in distinct endophenotypic changes of the adult offspring cerebral cortex independent of its current diet. The identified proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.

  15. Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

    Science.gov (United States)

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

  16. Calabash Chalk's Geophagy Affects Gestating Rats' Behavior and the Histomorphology of the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Moses B. Ekong

    2014-01-01

    Full Text Available Introduction. Calabash chalk contains heavy metals, and this lead to this study on the effect of this chalk on the behavior and the histomorphology of the cerebral cortex of gestating rats. Material & Methods. 24 female rats were equally divided into 4 groups and were mated at preostrous with the males. The day after mating was designated as day 1 of gestation. On gestation days 7–20, groups 1, 2, 3, and 4 animals were treated with 1 mL of distilled water, and 1 mL (200 mg/kg, 2 mL (400 mg/kg, and 3 mL (600 mg/kg of calabash chalk suspension, respectively. On pregnancy day 21, behavioral tests using the open field and the light/dark mazes were carried out and the animals subsequently euthanized and their brains were routinely processed. Results. There was no difference in ambulatory activities, but group 4 animals had more (P<0.05 transition frequency and were more averse to the dark in the light and dark field, while sections of the cerebral cortex showed a higher (P<0.05 cellular population, hypertrophied pyramidal cells, and vacuolations in the treatment groups. Conclusion. Calabash chalk may have anxiolytic effect especially at high dose in the light and dark field but not in the open field and can stimulate maternal cerebral cortical cellular changes.

  17. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Directory of Open Access Journals (Sweden)

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  18. Ethylmalonic acid modulates Na+, K(+)-ATPase activity and mRNA levels in rat cerebral cortex.

    Science.gov (United States)

    Schuck, Patrícia Fernanda; De Assis, Dênis Reis; Viegas, Carolina Maso; Pereira, Talita Carneiro Brandão; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Bogo, Mauricio Reis; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2013-03-01

    Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short-chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. In this work, we investigated the in vitro and in vivo EMA effects on Na(+), K(+)-ATPase (NAK) activity and mRNA levels in cerebral cortex from 30-day-old rats. For in vitro studies, cerebral cortex homogenates were incubated in the presence of EMA at 0.5, 1, or 2.5 mM concentrations for 1 h. For in vivo experiments, animals received three subcutaneous EMA injections (6 μmol g(-1); 90-min interval) and were killed 60 min after the last injection. After that, NAK activity and its mRNA expression were measured. We observed that EMA did not affect this enzyme activity in vitro. In contrast, EMA administration significantly increased NAK activity and decreased mRNA NAK expression as assessed by semiquantitative reverse transcriptase polymerase chain reaction when compared with control group. Considering the high score of residues prone to phosphorylation on NAK, this profile can be associated with a possible regulation by specific phosphorylation sites of the enzyme. Altogether, the present results suggest that NAK alterations may be involved in the pathophysiology of brain damage found in patients in which EMA accumulates. Copyright © 2012 Wiley Periodicals, Inc.

  19. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  20. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats

    Directory of Open Access Journals (Sweden)

    Siveshigan ePillay

    2014-02-01

    Full Text Available States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA and secondary visual (V2 cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5%, 4.5%, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness. Information integration was characterized by integration (multiinformation and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 x103 bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 x103 bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.

  1. Association of cerebral palsy with epilepsy.

    Science.gov (United States)

    Kaushik, A; Agarwal, R P; Sadhna

    1997-10-01

    Fifty patients of various types of cerebral palsy were studied to find out an association between cerebral palsy, EEG abnormalities and development quotient. Seventy-six per cent patients had spastic cerebral palsy. Hypotonic cerebral palsy was the next common type (14%). Athetosis and ataxic forms were found to be rare (2% each). Epilepsy was associated with 56% patients. Clinical types of seizures observed were: Generalised tonic-clonic (43%), myoclonic (17.9%), generalised tonic (10.7%), partial simple (10.7%) and partial complex (17.9%). The incidence of seizures was highest in hypotonic type in which 85.7% had epilepsy. Mean developmental quotient of cerebral palsy patients was 34.9% with maximum retardation in hypotonic cerebral palsy (25.14%). Sixty per cent of patients had abnormal EEG, out of these hypotonic patients had maximum (70%) chances of EEG abnormality followed by spastic patients (55%). Developmental retardation was more severe statistically in the patients with abnormal EEG than normal EEG.

  2. Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex

    Science.gov (United States)

    Lacoste, Baptiste; Comin, Cesar H.; Ben-Zvi, Ayal; Kaeser, Pascal S.; Xu, Xiaoyin; Costa, Luciano da F.; Gu, Chenghua

    2014-01-01

    SUMMARY Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals a novel feature of neurovascular interactions. PMID:25155955

  3. Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex.

    Science.gov (United States)

    Lacoste, Baptiste; Comin, Cesar H; Ben-Zvi, Ayal; Kaeser, Pascal S; Xu, Xiaoyin; Costa, Luciano da F; Gu, Chenghua

    2014-09-03

    Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether or not neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals an important feature of neurovascular interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  5. [The expressional alterations of CSF-1R after ischemic injury of cerebral cortex].

    Science.gov (United States)

    Yu, Dong Hui; Liu, Shuang; Tian, Zeng-Min; Liu, Shu-Hong; Ge, Xue-Ming; Zhou, Chang-Man; Wang, Ya-Qi; Fan, Ming

    2008-02-01

    To observe the expressional alterations of colony stimulating factor-1 receptor (CSF-1R) after ischemic injury of cerebral cortex, and study the function of colony stimulating factor-1 (CSF-1)/CSF-1R signal during the process of ischemic injury and repair of central nervous system (CNS). We examined the distribution and expression of CSF-1R in normal brain tissues and ischemic brain tissues by immunohistology and Western blot analysis. The expression of CSF-1R in neurons could be up-regulated by ischemic injury in CNS. CSF-1/CSF-1R might take part in the process of ischemic injury and repair.

  6. Effect of camphor essential oil on rat cerebral cortex activity as manifested by fractal dimension changes

    Directory of Open Access Journals (Sweden)

    Grbić G.

    2008-01-01

    Full Text Available The aim of our study was to investigate the effect of camphor essential oil on rat cerebral cortex activity by fractal analysis. Fractal dimension (FD values of the parietal electrocortical activity were calculated before and after intra-peritoneal administration of camphor essential oil (450-675 μl/kg in anesthetized rats. Camphor oil induced seizure-like activity with single and multiple spiking of high amplitudes in the parietal electrocorticogram and occasional clonic limb convulsions. The FD values of cortical activity after camphor oil administration increased on the average. Only FD values of cortical ECoG sequences were lower than those before camphor oil administration.

  7. Effect of Skull Type on the Relative Size of Cerebral Cortex and Lateral Ventricles in Dogs

    DEFF Research Database (Denmark)

    Pilegaard, Anders M; Berendt, Mette; Holst, Pernille

    2017-01-01

    of age. We used a continuous variable, the cranial index (CrI) to indicate skull shape and compared it with MRI volume measurements derived using Cavalieri's principle. We found a negative correlation between CrI and the ratio of cortical to ventricular volume. Breeds with a high CrI (large laterolateral...... compared to rostrocaudal cranial cavity dimension) had a smaller ratio of cortical to ventricular volume (low C:V ratio) than breeds with lower CrI skull types. It is important to consider this effect of skull shape on the relative volume estimates of the cerebral cortex and ventricles when trying...

  8. PRETERM BIRTH ASSOCIATION WITH CEREBRAL PALSY

    Directory of Open Access Journals (Sweden)

    Srinivasa Rao

    2015-04-01

    Full Text Available INTRODUCTION: Cerebral palsy ( CP is a group of permanent movement disorders that appear in early childhood. Preterm birth is the birth of baby before 37 completed weeks, a full term birth is birth at 37 to 42 weeks of gestation . AIM: To show the extent of association of preterm deliveries as a risk factor in development of cerebral palsy. MATERIALS AND METHODS: This r etrospective cohort study was conducted by eliciting history from the mothers of 99 cerebral palsy children who w ere treated in Rani Chandra Mani Devi Hospital, Visakhapatnam, Andhra Pradesh, India. De tailed history was taken from the mothers of 99 cerebral palsy children who were treated in this hospital. History regarding the period of gestation at which the child was born (preterm or full term, any previous history of pre - term delivery or abortions, was obtained from the mothers and the data analyzed . RESULTS: From this study it was observed the proportional association of pre - term births to cerebral palsy is 33 out 99 i.e., about 33.33%, Of these 33 cerebral palsy children highest association being with birth at 28 wks gestation (51 %. This study also shows th at the mothers with a previous history of preterm delivery have 14.4 times higher risk of subsequent pre term delivery; those with previous history of abortions have 5.7 times risk of pre - term delivery than mothers without such history. CONCLUSION: From th is study it was concluded that the pre - term birth plays a major role as a risk factor in the development of cerebral palsy with mothers having previous pre term delivery and previous abortions adding further to this risk.

  9. Diffusion tensor imaging detects early cerebral cortex abnormalities in neuronal architecture induced by bilateral neonatal enucleation: An experimental model in the ferret

    Directory of Open Access Journals (Sweden)

    Andrew S Bock

    2010-10-01

    Full Text Available Diffusion tensor imaging (DTI is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA, that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7 in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally-adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally-enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy.

  10. Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy.

    Science.gov (United States)

    Leke, Renata; Escobar, Thayssa D C; Rao, Kakulavarapu V Rama; Silveira, Themis Reverbel; Norenberg, Michael D; Schousboe, Arne

    2015-09-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE. Under physiological conditions, glutamine is fundamental for replenishment of the neurotransmitter pools of glutamate and GABA. The different isoforms of glutamine transporters play an important role in the transfer of this amino acid between astrocytes and neurons. A disturbance in the GABA biosynthetic pathways has been described in bile duct ligated (BDL) rats, a well characterized model of chronic HE. Considering that glutamine is important for GABA biosynthesis, altered glutamine transport and the subsequent glutamate/GABA-glutamine cycle efficacy might influence these pathways. Given this potential outcome, the aim of the present study was to investigate whether the expression of the glutamine transporters SAT1, SAT2, SN1 and SN2 would be affected in chronic HE. We verified that mRNA expression of the neuronal glutamine transporters SAT1 and SAT2 was found unaltered in the cerebral cortex of BDL rats. Similarly, no changes were found in the mRNA level for the astrocytic transporter SN1, whereas the gene expression of SN2 was increased by two-fold in animals with chronic HE. However, SN2 protein immuno-reactivity did not correspond with the increase in gene transcription since it remained unaltered. These data indicate that the expression of the glutamine transporter isoforms is unchanged during chronic HE, and thus likely not to participate in the pathological mechanisms related to the imbalance in the GABAergic neurotransmitter system observed in this neurologic condition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Gerstmann's syndrome associated with diagnostic cerebral angiography.

    Science.gov (United States)

    Wu, Yung-Tsan; Chen, Liang-Cheng; Lin, Shu-Lin; Chang, Shin-Tsu

    2013-01-01

    Gerstmann's syndrome is a rare neurological disorder characterized by right-left disorientation, finger agnosia, agraphia and acalculia. Several causes for the manifestation of this rare syndrome have been reported in previous publications; however, thus far, an association between secondary diagnostic cerebral angiography and Gerstmann's syndrome has not been reported. A 48-year-old woman diagnosed with subarachnoid haemorrhage underwent a secondary diagnostic cerebral angiography 7 months after the episode. The patient showed memory impairment, agraphia, acalculia, right-left disorientation, occasional errors in speech and finger agnosia accompanied by an acute infarction in the left middle cerebral artery territory. However, she showed excellent recovery after intensive rehabilitation and conservative treatment. The previously reported rate of permanent neurological complications associated with diagnostic cerebral angiography was very low (0-0.5%). To the best of the authors' knowledge, this is the first case report of Gerstmann's syndrome as a complication of cerebral angiography. This report discusses the complications associated with the neurological condition and emphasizes the need for early rehabilitation in cases of Gerstmann's syndrome.

  12. Does Cell Lineage in the Developing Cerebral Cortex Contribute to its Columnar Organization?

    Science.gov (United States)

    Costa, Marcos R.; Hedin-Pereira, Cecilia

    2010-01-01

    Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone (VZ) could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighboring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell–cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits. PMID:20676384

  13. Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals

    Directory of Open Access Journals (Sweden)

    Yohei Shinmyo

    2017-08-01

    Full Text Available Folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. However, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. By combining in utero electroporation and the CRISPR/Cas9 system, we succeeded in efficient gene knockout of Cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencephalic brains of ferrets. We show that Cdk5 knockout in the ferret cerebral cortex markedly impaired cortical folding. Furthermore, the results obtained from the introduction of dominant-negative Cdk5 into specific cortical layers suggest that Cdk5 function in upper-layer neurons is more important for cortical folding than that in lower-layer neurons. Cdk5 inhibition induced severe migration defects in cortical neurons. Taken together, our findings suggest that the appropriate positioning of upper-layer neurons is critical for cortical folding.

  14. Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study

    Directory of Open Access Journals (Sweden)

    Aysel Agar

    2011-08-01

    Full Text Available The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n=12 for 10 days; CG-15, n=12 for 15 days; CG-20, n=12 for 20 days. The three experimental groups (EG-10, n=12; EG-15, n=12; EG-20, n=12 were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10, 15 days (EG-15 and 20 days (EG-20. Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (p<0.05. However, synaptic density was significantly decreased in the experimental groups as compared to the control groups (p<0.05. The results suggest that the excess of vitamin B6 intake causes damage to the cerebral cortex due to cellular intoxication and decreased synaptic density. Thus, careful attention should be paid to the time and dose of vitamin B6 recommended for patients who are supplemented with this vitamin

  15. Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.

    Science.gov (United States)

    Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato

    2017-01-29

    Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Causal interactions between the cerebral cortex and the autonomic nervous system.

    Science.gov (United States)

    Yu, XiaoLin; Zhang, Chong; Zhang, JianBao

    2014-05-01

    Mental states such as stress and anxiety can cause heart disease. On the other hand, meditation can improve cardiac performance. In this study, the heart rate variability, directed transfer function and corrected conditional entropy were used to investigate the effects of mental tasks on cardiac performance, and the functional coupling between the cerebral cortex and the heart. When subjects tried to decrease their heart rate by volition, the sympathetic nervous system was inhibited and the heart rate decreased. When subjects tried to increase their heart rate by volition, the parasympathetic nervous system was inhibited and the sympathetic nervous system was stimulated, and the heart rate increased. When autonomic nervous system activity was regulated by mental tasks, the information flow from the post-central areas to the pre-central areas of the cerebral cortex increased, and there was greater coupling between the brain and the heart. Use of directed transfer function and corrected conditional entropy techniques enabled analysis of electroencephalographic recordings, and of the information flow causing functional coupling between the brain and the heart.

  17. Epigallocatechin-3-gallate attenuates acrylamide-induced apoptosis and astrogliosis in rat cerebral cortex.

    Science.gov (United States)

    He, Yin; Tan, Dehong; Bai, Bing; Wu, Zhaoxia; Ji, Shujuan

    2017-05-01

    The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2'-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR-treated rats. Analysis of DNA fragmentation and protein expression of Bax, Bcl-2, caspase 3, and cytochrome c revealed that EGCG inhibited ACR-induced apoptosis. Furthermore, EGCG inhibited oxidative stress by enhancing the activity of antioxidant enzymes and glutathione levels and reducing the formation of reactive oxygen species and lipid peroxidation. Taken together, our data demonstrate that EGCG inhibits ACR-induced apoptosis and astrogliosis in the cerebral cortex.

  18. Altered muscarinic receptor expression in the cerebral cortex of epileptic rats: Restorative role of Withania somnifera.

    Science.gov (United States)

    Anju, T R; Smijin, S; Mathew, Jobin; Paulose, C S

    2017-12-07

    Temporal Lobe Epilepsy involves a sequence of events which can lead to neurotransmitter signalling alterations. Many herbal extracts are considered as alternative therapeutic method for epilepsy management. In the present study, we investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in the management of Temporal Lobe Epilepsy. Confocal imaging of TOPRO-3 stained cortical sections showed severe damage in epileptic brain. We also observed a reduced antioxidant potential and increased peroxide level in epileptic group. Oxidative stress resulted in the down regulation of CREB, NF-κB and TNF-α with an up regulation of the apoptotic factors Caspase 8, 3 and bax in epileptic group. Epileptic condition also resulted in an increased muscarinic receptor binding and mRNA expression in the cerebral cortex. Withania somnifera and Withanolide A significantly reversed the altered muscarinic receptor expression and reversed the oxidative stress and resultant derailment in cell signalling. Thus our studies suggest that Withania somnifera and Withanolide A play an important role in central muscarinic receptor functional balance and activation of antioxidant system in the cerebral cortex of temporal lobe epileptic condition. These findings can be of immense therapeutic significance for epileptic management.

  19. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  20. Does cell lineage in the developing cerebral cortex contribute to its columnar organization?

    Directory of Open Access Journals (Sweden)

    Marcos R Costa

    2010-06-01

    Full Text Available Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighbouring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell-cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits.

  1. Functional activation of the cerebral cortex related to sensorimotor adaptation of reactive and voluntary saccades.

    Science.gov (United States)

    Gerardin, Peggy; Miquée, Aline; Urquizar, Christian; Pélisson, Denis

    2012-07-16

    Potentially dangerous events in the environment evoke automatic ocular responses, called reactive saccades. Adaptation processes, which maintain saccade accuracy against various events (e.g. growth, aging, neuro-muscular lesions), are to date mostly relayed to cerebellar activity. Here we demonstrate that adaptation of reactive saccades also involves cerebral cortical areas. Moreover, we provide the first identification of the neural substrates of adaptation of voluntary saccades, representing the complement to reactive saccades for the active exploration of our environment. An fMRI approach was designed to isolate adaptation from saccade production: an adaptation condition in which the visual target stepped backward 50 ms after saccade termination was compared to a control condition where the same target backstep occurred 500 ms after saccade termination. Subjects were tested for reactive and voluntary saccades in separate sessions. Multi-voxel pattern analyses of fMRI data from previously-defined regions of interests (ROIs) significantly discriminated between adaptation and control conditions for several ROIs. Some of these areas were revealed for adaptation of both saccade categories (cerebellum, frontal cortex), whereas others were specifically related to reactive saccades (temporo-parietal junction, hMT+/V5) or to voluntary saccades (medial and posterior areas of intra-parietal sulcus). These findings critically extend our knowledge on brain motor plasticity by showing that saccadic adaptation relies on a hitherto unknown contribution of the cerebral cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Expression of sarcoglycans in the human cerebral cortex: an immunohistochemical and molecular study.

    Science.gov (United States)

    Anastasi, Giuseppe; Tomasello, Francesco; Di Mauro, Debora; Cutroneo, Giuseppina; Favaloro, Angelo; Conti, Alfredo; Ruggeri, Alessia; Rinaldi, Carmela; Trimarchi, Fabio

    2012-01-01

    The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, β, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses. Copyright © 2012 S. Karger AG, Basel.

  3. Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2013-01-01

    in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels...

  4. The lizard cerebral cortex as a model to study neuronal regeneration

    Directory of Open Access Journals (Sweden)

    CARLOS LOPEZ-GARCIA

    2002-03-01

    Full Text Available The medial cerebral cortex of lizards, an area homologous to the hippocampal fascia dentata, shows delayed postnatal neurogenesis, i.e., cells in the medial cortex ependyma proliferate and give rise to immature neurons, which migrate to the cell layer. There, recruited neurons differentiate and give rise to zinc containing axons directed to the rest of cortical areas, thus resulting in a continuous growth of the medial cortex and its zinc-enriched axonal projection. This happens along the lizard life span, even in adult lizards, thus allowing one of their most important characteristics: neuronal regeneration. Experiments in our laboratory have shown that chemical lesion of the medial cortex (affecting up to 95% of its neurons results in a cascade of events: first, massive neuronal death and axonal-dendritic retraction and, secondly, triggered ependymal-neuroblast proliferation and subsequent neo-histogenesis and regeneration of an almost new medial cortex, indistinguishable from a normal undamaged one. This is the only case to our knowledge of the regeneration of an amniote central nervous centre by new neuron production and neo-histogenesis. Thus the lizard cerebral cortex is a good model to study neuronal regeneration and the complex factors that regulate its neurogenetic, migratory and neo-synaptogenetic events.O córtex cerebral de lagartos, uma área homóloga à fascia dentata hipocampal, exibe neurogênese pós-natal prolongada, isto é, o epêndima do córtex medial prolifera e dá origem a neurônios imaturos, que migram para a camada celular. Nesta camada, neurônios recrutados se diferenciam e dão origem a axônios, ricos em zinco, que se projetam para as demais áreas corticais, do que resulta um crescimento contínuo do córtex medial e sua projeção axonal. Isto acontece por toda a vida do lagarto, mesmo em animais adultos, o que permite uma de suas características mais importantes: a regeneração neuronal. Experimentos em

  5. Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study.

    Science.gov (United States)

    Deng, Xiaofeng; Zhang, Yan; Xu, Long; Wang, Bo; Wang, Shuo; Wu, Jun; Zhang, Dong; Wang, Rong; Wang, Jia; Zhao, Jizong

    2015-05-01

    OBJECT Cerebral arteriovenous malformations (AVMs) are congenital malformations that may grow in the language cortex but usually do not lead to aphasia. In contrast, language dysfunction is a common presentation for patients with a glioma that involves language areas. The authors attempted to demonstrate the difference in patterns of language cortex reorganization between cerebral AVMs and gliomas by blood oxygen level-dependent (BOLD) functional MRI (fMRI) evaluation. METHODS The authors retrospectively reviewed clinical and imaging data of 63 patients with an unruptured cerebral AVM (AVM group) and 38 patients with a glioma (glioma group) who underwent fMRI. All the patients were right handed, and all their lesions were located in the left cerebral hemisphere. Patients were further categorized into 1 of the 2 following subgroups according to their lesion location: the BA subgroup (overlying or adjacent to the inferior frontal or the middle frontal gyri [the Broca area]) and the WA subgroup (overlying or adjacent to the supramarginal, angular, or superior temporal gyri [the Wernicke area]). Lateralization indices of BOLD signal activations were calculated separately for the Broca and Wernicke areas. Statistical analysis was performed to identify the difference in patterns of language cortex reorganization between the 2 groups. RESULTS In the AVM group, right-sided lateralization of BOLD signal activations was observed in 23 patients (36.5%), including 6 with right-sided lateralization in the Broca area alone, 12 in the Wernicke area alone, and 5 in both areas. More specifically, in the 34 patients in the AVM-BA subgroup, right-sided lateralization of the Broca area was detected in 9 patients (26.5%), and right-sided lateralization of the Wernicke area was detected in 4 (11.8%); in the 29 patients in the AVM-WA subgroup, 2 (6.9%) had right-sided lateralization of the Broca area, and 13 (44.8%) had right-sided lateralization of the Wernicke area. In the glioma group

  6. Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the Rat Cerebral Cortex.

    Science.gov (United States)

    Lameth, Julie; Gervais, Annie; Colin, Catherine; Lévêque, Philippe; Jay, Thérèse M; Edeline, Jean-Marc; Mallat, Michel

    2017-10-01

    Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

  7. [Effect of basic fibroblast growth factor on endogenous neural stem cell in rat cerebral cortex with global cerebral ischemia-reperfusion].

    Science.gov (United States)

    Ren, Mingxin; Deng, Xiaohui; Guo, Yiwei; Zheng, Fengjin; Feng, Zhibo

    2014-08-01

    The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.

  8. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  9. Role of mechanical factors in the morphology of the primate cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Claus C Hilgetag

    2006-03-01

    Full Text Available The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical development based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.

  10. [Changes in the cerebral cortex in closed craniocerebral trauma of gunshot origin (experimental research)].

    Science.gov (United States)

    Novozhilova, A P; Dyskin, E A; Isakov, V D; Kolkutin, V V

    1996-01-01

    Cerebral cortex was studied morphologically in rabbits with concussion of brain induced by gunshot injury. The extent of severity was modelled by the bullet rate. No significant bleeding followed the injury allowing to observe the animals during the necessary terms (7-14 d.) Morphological study included light optical and electron microscopy. In neurons, glial cells and synapses a series of essential destructive changes in shown detectable predominantly on ultrastructural level that might be the base of psychoneurological complications of a distant period. Ballistic properties of a bullet were obviously fundamental to pathogenesis of brain concussion in these experiments as kinetic energy of the bullet was only sufficient for non significant damage of the skull soft tissue. But in contrast to the dull trauma, the blow was of a high speed and despite mild clinical characteristics caused essential diffuse structural disturbances in brain tissues.

  11. Dependence of cerebral-cortex activation in women on environmental factors

    Science.gov (United States)

    Pavlov, K. I.; Mukhin, V. N.; Kamenskaya, V. G.; Klimenko, V. M.

    2016-12-01

    The investigation of female physiological reactions to different meteorological conditions and space weather is relevant, since there are little experimental findings in this field. The purpose of this work is to determine how the level of cerebral-cortex activity in women depends on the meteorological and cosmophysical parameters of weather and space processes. We studied electroencephalograms (EEGs) recorded at rest in the sitting position and with eyes closed. We performed four series of measurements of brain bioelectrical activity from February to June 2013. We found that the level of cortical activity recorded by EEG changed significantly during these 6 months. Significant differences were detected between the cortical activity and the parameters of weather and space processes; namely, an increase in the air temperature and a decrease in the wind speed and cosmic-ray energy result in a decrease in the activity rate of the right occipital lobe.

  12. Specification of excitatory neurons in the developing cerebral cortex: progenitor diversity and environmental influences.

    Science.gov (United States)

    Costa, Marcos R; Müller, Ulrich

    2014-01-01

    The mature cerebral cortex harbors a heterogeneous population of glutamatergic neurons, organized into a highly intricate histological architecture. Classically, this mixed population of neurons was thought to be generated sequentially from a seemingly homogenous group of progenitors under the influence of external cues. This view, however, has been challenged in the last decade by evidences pointing to the existence of fate-restricted neuronal progenitors in the developing neocortex. Here, we review classical studies using cell transplantation, retroviral labeling and cell culture, as well as new data from genetic fate-mapping analysis, to discuss the lineage relationships between neocortical progenitors and subclasses of excitatory neurons. We also propose a temporal model to conciliate the existence of fate-restricted progenitors alongside multipotent progenitors in the neocortex. Finally, we discuss evidences for a critical period of plasticity among post mitotic excitatory cortical neurons when environmental influences could change neuronal cell fate.

  13. Physiology, anatomy, and plasticity of the cerebral cortex in relation to musical instrument performance

    Science.gov (United States)

    Tramo, Mark Jude

    2004-05-01

    The acquisition and maintenance of fine-motor skills underlying musical instrument performance rely on the development, integration, and plasticity of neural systems localized within specific subregions of the cerebral cortex. Cortical representations of a motor sequence, such as a sequence of finger movements along the keys of a saxophone, take shape before the figure sequence occurs. The temporal pattern and spatial coordinates are computed by networks of neurons before and during the movements. When a finger sequence is practiced over and over, performance gets faster and more accurate, probably because cortical neurons generating the sequence increase in spatial extent, their electrical discharges become more synchronous, or both. By combining experimental methods such as single- and multi-neuron recordings, focal stimulation, microanatomical tracers, gross morphometry, evoked potentials, and functional imaging in humans and nonhuman primates, neuroscientists are gaining insights into the cortical physiology, anatomy, and plasticity of musical instrument performance.

  14. Parvalbumin and calbindin immunoreactivity in the cerebral cortex of the hedgehog (Erinaceus europaeus).

    Science.gov (United States)

    Ferrer, I; Zujar, M J; Admella, C; Alcantara, S

    1992-01-01

    To investigate the morphology and distribution of nonpyramidal neurons in the brain of insectivores, parvalbumin and calbindin 28 kDa immunoreactivity was examined in the cerebral cortex of the hedgehog (Erinaceus europaeus). Parvalbumin-immunoreactive cells were found in all layers of the isocortex, but in contrast to other mammals, a laminar organisation or specific regional distribution was not seen. Characteristic parvalbumin-immunoreactive neurons were multipolar cells with large ascending and descending dendrites extending throughout several layers. Calbindin-immunoreactive neurons were similar to those found in other species, although appearing in smaller numbers than in the cerebral cortex of more advanced mammals. The morphology and distribution of parvalbumin- and calbindin-immunoreactive cells in the piriform and entorhinal cortices were similar in hedgehogs and rodents. Parvalbumin-immunoreactive cells in the hippocampal complex were pyramidal-like and bitufted neurons, which were mainly found in the stratum oriens and stratum pyramidale of the hippocampus, and in the stratum moleculare and hilus of the fascia dentata. Heavily stained cells were found in the deep part of the stratum granulare. Intense calbindin immunoreactivity occurred mainly in the granule cell and molecular layers of the dentate gyrus and in the mossy fibre layer. The most outstanding feature in the hippocampal complex of the hedgehog was the extension of calbindin immunoreactivity to CA1 field of the hippocampus, suggesting, in agreement with other reports, that mossy fibres can establish synaptic contacts throughout the pyramidal cell layer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1452472

  15. Edible Camphor-induced Histopathological Changes in Hippocampus and Cerebral Cortex Following Oral Administration into Rats

    Directory of Open Access Journals (Sweden)

    Oluwatobi T Somade

    2017-03-01

    Full Text Available Introduction: Raw edible camphor (EC, and as component of herbal infusions are widely used to treat pile, back pain, erectile dysfunction, and as an aphrodisiac especially in preparation for sexual intercourse by men. It has been traced in umbilical cord, blood, fetal, adipose, and other tissues including brain, where it bioaccumulates. Methods: The study, therefore, investigated the possible histopathological changes in brain, heart, and spleen that may result following EC administration in rats. Thirty animals were used for the study and were divided into six groups of five rats each. Group I animals served as normal control, Group II animals served as vehicle control and were orally administered 6 mL/kg corn oil daily for 7 days, while Groups III-VI animals were orally administered 1, 2, 4, and 6 g/kg EC for 7 days daily. Results and Conclusions: Following the administrations of various doses of EC, the histopathological changes seen in the cerebral cortex of the brain include mild submeningeal spongiosis, mild diffuse spongiosis of the parenchyma, a very mild diffuse gliosis, and presences of gitter cells, while in hippocampus, there were mild diffuse gliosis and disruption of the progression of the hippocampal horns, as well as foci of spongiosis around the hippocampal horns, and neuronal cells have open faced nuclei. No effect was seen in heart and spleen except 4 g/kg of EC that revealed moderate diffuse congestion in spleen only. In conclusion, EC may not have any toxic effects on the cardiac and splenic cells, but had toxic effects on the brain hippocampus and cerebral cortex, and may lead to brain cell damage. [J Interdiscipl Histopathol 2017; 5(1.000: 7-11

  16. Consciousness without a cerebral cortex: a challenge for neuroscience and medicine.

    Science.gov (United States)

    Merker, Bjorn

    2007-02-01

    A broad range of evidence regarding the functional organization of the vertebrate brain - spanning from comparative neurology to experimental psychology and neurophysiology to clinical data - is reviewed for its bearing on conceptions of the neural organization of consciousness. A novel principle relating target selection, action selection, and motivation to one another, as a means to optimize integration for action in real time, is introduced. With its help, the principal macrosystems of the vertebrate brain can be seen to form a centralized functional design in which an upper brain stem system organized for conscious function performs a penultimate step in action control. This upper brain stem system retained a key role throughout the evolutionary process by which an expanding forebrain - culminating in the cerebral cortex of mammals - came to serve as a medium for the elaboration of conscious contents. This highly conserved upper brainstem system, which extends from the roof of the midbrain to the basal diencephalon, integrates the massively parallel and distributed information capacity of the cerebral hemispheres into the limited-capacity, sequential mode of operation required for coherent behavior. It maintains special connective relations with cortical territories implicated in attentional and conscious functions, but is not rendered nonfunctional in the absence of cortical input. This helps explain the purposive, goal-directed behavior exhibited by mammals after experimental decortication, as well as the evidence that children born without a cortex are conscious. Taken together these circumstances suggest that brainstem mechanisms are integral to the constitution of the conscious state, and that an adequate account of neural mechanisms of conscious function cannot be confined to the thalamocortical complex alone.

  17. Association between type of cerebral palsy and the cognitive levels

    Directory of Open Access Journals (Sweden)

    Ratna Dewi Kusumaningrum

    2009-07-01

    Conclusion Our data showed that most patients with cerebral palsy had mental retardation of several cognitive level but there was no significant association between each type of cerebral palsy with cognitive levels.

  18. The effect of imipramine on lipid peroxidation in the rat cerebral cortex.

    Science.gov (United States)

    Melzacka, M; Sas-Korczyńska, A; Syrek, M

    1995-01-01

    The effect of imipramine (IMI) on lipid peroxidation in the rat cerebral cortex was investigated in ex vivo and in vitro study. It was found that IMI when given to rats chronically (14 x 10 mg/kg ip) but not acutely (10 mg/kg ip), inhibited lipid peroxidation in the cortical membranes of rat brain. When added in different concentrations (0.125-10.0 nmoles/sample) to the cerebral cortical membranes of naive rats in vitro, IMI inhibited lipid peroxidation in concentration-dependent fashion. Using [3H]-IMI it was found that employed procedure for membrane preparation did not removed IMI from cortical membranes of rats treated chronically with the drug and this might explain the lack of antioxidant effect of IMI in animals treated with a single dose of IMI in ex vivo study. A comparative study of IMI and chlorpromazine (CPZ)-whose inhibitory effect on the free radicals formation has been found before-indicated the higher potency of IMI than that of CPZ as radical scavenger in ex vivo and in vitro studies. The results imply that IMI might affect the brain function also through its effect on lipid peroxidation.

  19. Numeric and symbolic knowledge representation of cerebral cortex anatomy: methods and preliminary results.

    Science.gov (United States)

    Dameron, O; Gibaud, B; Morandi, X

    2004-06-01

    The human cerebral cortex anatomy describes the brain organization at the scale of gyri and sulci. It is used as landmarks for neurosurgery as well as localization support for functional data analysis or inter-subject data comparison. Existing models of the cortex anatomy either rely on image labeling but fail to represent variability and structural properties or rely on a conceptual model but miss the inner 3D nature and relations of anatomical structures. This study was therefore conducted to propose a model of sulco-gyral anatomy for the healthy human brain. We hypothesized that both numeric knowledge (i.e., image-based) and symbolic knowledge (i.e., concept-based) have to be represented and coordinated. In addition, the representation of this knowledge should be application-independent in order to be usable in various contexts. Therefore, we devised a symbolic model describing specialization, composition and spatial organization of cortical anatomical structures. We also collected numeric knowledge such as 3D models of shape and shape variation about cortical anatomical structures. For each numeric piece of knowledge, a companion file describes the concept it refers to and the nature of the relationship. Demonstration software performs a mapping between the numeric and the symbolic aspects for browsing the knowledge base.

  20. Significance of F3/Contactin gene expression in cerebral cortex and nigrostriatal development.

    Science.gov (United States)

    Massaro, Antonio; Bizzoca, Antonella; Corsi, Patrizia; Pinto, Marco F; Carratù, Maria Rosaria; Gennarini, Gianfranco

    2012-07-01

    F3/Contactin is a neuronal surface glycoprotein, which plays a general role in neural development and, in particular, in neuronal and oligodendrocyte differentiation. In a previous study using the F3/EGFP transgenic mice, which express an EGFP reporter under control of the regulatory region from the mouse F3/Contactin gene, the activation of the F3/Contactin promoter was found to correlate with granule and Purkinje neuron differentiation in developing cerebellar cortex. Here we report that in developing cerebral cortex and basal ganglia the F3/Contactin gene is mostly activated during early commitment of neuronal precursors, thus indicating a region-specific profile of its developmental activation. We also report that, in the same structures of F3/EGFP mice, a downregulation of the endogenous F3/Contactin gene occurs, which correlates with upregulation of the dopaminergic phenotype and with locomotor pattern abnormalities. Therefore, F3/EGFP transgenic mice exhibit morphological and functional phenotypes recapitulating those arising from imbalance of the striatal dopaminergic pathway. As for the underlying mechanisms, we postulate that in F3/EGFP mice F3/Contactin downregulation results from the ability of transgene promoter sequences to interfere with the activation of the endogenous gene, thus realizing an F3/Contactin knockdown model, while dopaminergic upregulation is consistent with a general F3/Contactin inhibitory effect on the neuronal phenotype. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Promising techniques to illuminate neuromodulatory control of the cerebral cortex in sleeping and waking states.

    Science.gov (United States)

    Kanda, Takeshi; Ohyama, Kaoru; Muramoto, Hiroki; Kitajima, Nami; Sekiya, Hiroshi

    2017-05-01

    Sleep, a common event in daily life, has clear benefits for brain function, but what goes on in the brain when we sleep remains unclear. Sleep was long regarded as a silent state of the brain because the brain seemingly lacks interaction with the surroundings during sleep. Since the discovery of electrical activities in the brain at rest, electrophysiological methods have revealed novel concepts in sleep research. During sleep, the brain generates oscillatory activities that represent characteristic states of sleep. In addition to electrophysiology, opto/chemogenetics and two-photon Ca2+ imaging methods have clarified that the sleep/wake states organized by neuronal and glial ensembles in the cerebral cortex are transitioned by neuromodulators. Even with these methods, however, it is extremely difficult to elucidate how and when neuromodulators spread, accumulate, and disappear in the extracellular space of the cortex. Thus, real-time monitoring of neuromodulator dynamics at high spatiotemporal resolution is required for further understanding of sleep. Toward direct detection of neuromodulator behavior during sleep and wakefulness, in this review, we discuss developing imaging techniques based on the activation of G-protein-coupled receptors that allow for visualization of neuromodulator dynamics. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  2. Vibrissaeless mutant rats with a modular representation of innervated sinus hair follicles in the cerebral cortex.

    Science.gov (United States)

    Kuljis, R O

    1992-01-01

    Specialized areas in the cerebral cortex are essential to mediate the various sensory modalities and are crucial to their recovery in disease. We recently observed that prenatal photoreceptor cues are not indispensable for the development of the elaborate modular organization of the primate primary visual (striate) cortex (Kuljis, R. O. and P. Rakic. 1990. Proc. Natl. Acad. Sci. USA 87: 5303-5306). By contrast, the elegant experiments of Woolsey, Van der Loos, and collaborators (Van der Loos, H., and T. A. Woolsey. 1973. Science 179: 395-398; Van der Loos, H. and J. Dörfl. 1978. Neurosci Lett. 7: 23-30; Woolsey, T. A. 1967. John Hopkins Med. J. 121: 91-112; Woolsey, T. A. and H. Van der Loos. 1970. Brain Res. 17: 205-242) indicate that postnatal vibrissal receptor input is necessary for the development of modular organization in the posteromedial barrel subfield (PMBSF) of the rodent somatosensory cortex. The present report is part of a series of studies designed to address the variables that result in seemingly different results in these two models. Here, I address the role of pre- and postnatal tactile experience in the development of the rat homologue of the mouse PMBSF using mutants that lack vibrissae. Mutants exhibit cytoarchitectonic units in layer IV similar to those in controls, as revealed by NissI stains and histochemistry for succinate dehydrogenase and cytochrome oxidase. Sections from flat mounts of the vibrissal pad reveal that all mutants contain vibrissal follicles with stumps of sinus hairs in a geometric array and number similar to that in controls, and that the follicles are innervated heavily by fascicles of fibers from the infraorbital nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Spatiotemporal profiles of dental pulp nociception in rat cerebral cortex: an optical imaging study.

    Science.gov (United States)

    Nakamura, Hiroko; Kato, Risako; Shirakawa, Tetsuo; Koshikawa, Noriaki; Kobayashi, Masayuki

    2015-06-01

    Somatosensation is topographically organized in the primary (S1) and secondary somatosensory cortex (S2), which contributes to identify the region receiving sensory inputs. However, it is still unknown how somatosensory inputs from the oral region, especially nociceptive inputs from the teeth, are processed in the somatosensory cortex. We performed in vivo optical imaging and identified the precise cortical regions responding to electrical stimulation of the maxillary and mandibular dental pulp in rats. Electrical stimulation of the mandibular incisor pulp evoked neural excitation in two areas: the most rostroventral part of S1, and the ventral part of S2 caudal to the middle cerebral artery. Maxillary incisor pulp stimulation initially evoked responses only in the ventral part of S2, although later maximum responses were also observed in S1 similar to mandibular incisor stimulation responses. The maxillary and mandibular molar pulp-responding regions were located in the most ventral S2, a part of which was histologically classified as the insular oral region (IOR). In terms of the initial responses, maxillary incisor and molar stimulation induced excitation in the S2/IOR rostral to the mandibular dental pulp-responding region. Contrary to the spatially segregated initial responses, the maximum excitatory areas responding to both incisors and molars in the mandible and maxilla overlapped in S1 and the S2/IOR. Multielectrode extracellular recording supported the characteristic localization of S2/IOR neurons responding to mandibular and maxillary molar pulp stimulation. The discrete and overlapped spatial profiles of initial and maximum responses, respectively, may characterize nociceptive information processing of dental pain in the cortex. © 2015 Wiley Periodicals, Inc.

  4. Stem/progenitor cells in the cerebral cortex of the human preterm: a resource for an endogenous regenerative neuronal medicine?

    Directory of Open Access Journals (Sweden)

    Laura Vinci

    2016-04-01

    Full Text Available The development of the central nervous system represents a very delicate period of embryogenesis. Premature interruption of neurogenesis in human preterm newborns can lead to motor deficits, including cerebral palsy, and significant cognitive, behavioral or sensory deficits in childhood. Preterm infants also have a higher risk of developing neurodegenerative diseases later in life. In the last decade, great importance has been given to stem/progenitor cells and their possible role in the development and treatment of several neurological disorders. Several studies, mainly carried out on experimental models, evidenced that immunohistochemistry may allow the identification of different neural and glial precursors inside the developing cerebral cortex. However, only a few studies have been performed on markers of human stem cells in the embryonic period.This review aims at illustrating the importance of stem/progenitor cells in cerebral cortex during pre- and post-natal life. Defining the immunohistochemical markers of stem/progenitor cells in the human cerebral cortex during development may be important to develop an “endogenous” target therapy in the perinatal period. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  5. [Effect of acupuncture intervention on 14-3-3 expression in cerebral cortex of hypoxic-ischemic brain damage rats].

    Science.gov (United States)

    Li, Xing-er; Yuan, Qing; Tang, Chun-zhi; Chen, Fei; Zhao, Rong; Liu, Long-lin; Yu, Yu-tian; Cao, Yong; Wu, Jia-li; Sun, Shuo

    2014-12-01

    To observe the effect of acupuncture therapy on 14-3-3, Bcl-2 and Bax expression levels in the cerebral cortex in neonatal rats with hypoxic-ischemic brain damage(HIBD). Timed pregnant Sprague-Dawley rat dams were delivered either vaginally (normal group), or by C-section (sham-operation group) or by C-section with 5 min of global anoxia (anoxia group), with 8 rats in each group. The rat pups of the anoxia group were randomly divided into model group and acupuncture group (n =8). Acupuncture stimulation of "Naosanzhen" "Niesanzhen" and "Zhisanzhen" acupoints was given begin- ning from the 14th day after birth, once daily for 7 consecutive days. All rat pups were killed by decapitation on day 21 after birth, and then 14-3-3, Bcl-2 and Bax immunoactivity (expression) in the cerebral cortex were detected by immunohistochemistry. In comparison with the normal group, the expression level of cerebral cortical 14-3-3 was significantly decreased, and that of Bax remarkably increased in the model group (Poperation group (P0. 05). Acupuncture intervention can increase the expression of 14-3-3 and Bcl-2 in the cerebral cortex in HIBD rats.

  6. The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J. A.; Son, H. S.; Kim, S. H.; Jung, S. G [The Catholic University of Korea, Seoul (Korea, Republic of)

    2004-07-01

    Authors report the effectiveness of MCS in extraordinarily extended pain due to intractable CRPS type II and rCBF study result for mechanism of pain control by MCS. A 43-year-old male presented severe spontaneous burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. Authors planned MCS as a neuromodulation therapy for this intractable peripheral neuropathic pain patient because further neurodestructive procedure did not work anymore and have a potential risk of further aggrevation of neuopathic pain. We performed baseline and stimulation brain perfusion SPECT using 20 mCi of Tc-99m ECD. The baseline CBD studies were done with stimulator 'off' state and stimulation studies were done after stimulator 'on' with satisfactory pain relief. For the stimulation study, the radioisotope was injected immediately after pain-relief and the images were taken about 50 minutes after injection of radioisotope. In resting rCBF in the patient was compared with normal control datas, we found significant increase in rCBF in the bilateral prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, left temporooccipital area. When rCBF datas obtained after alleviation of pain with stimulator 'on' . there were significant increase in rCBF in bilateral prefrontal cortex and left temporoocipital area. After subtraction of ECD SPECT, we found significant increase in rCBF in the right premotor and supplementary motor cortex left sensorimotor cortex, right cingulated cortex, right posterior insular cortex, right anterior limb of internal capsule. left orbitofrontal cortex and right pyramidal tract in cerebral peduncle. Authors report exellent pain control by MCS in a case of severe CRPS type II with hemibody involvement and regional cerebral blood flow changes according to successful pain control.

  7. Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorders

    Directory of Open Access Journals (Sweden)

    David Vállez García

    2016-08-01

    Full Text Available There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD. However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1 to validate previous results showing alterations of regional cerebral blood flow (rCBF in cWAD, (2 to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3 to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H215O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.

  8. A novel synaptic vesicle fusion path in the rat cerebral cortex: the "saddle" point hypothesis.

    Science.gov (United States)

    Zampighi, Guido A; Serrano, Raul; Vergara, Julio L

    2014-01-01

    We improved freeze-fracture electron microscopy to study synapses in the neuropil of the rat cerebral cortex at ∼2 nm resolution and in three-dimensions. In the pre-synaptic axon, we found that "rods" assembled from short filaments protruding from the vesicle and the plasma membrane connects synaptic vesicles to the membrane of the active zone. We equated these "connector rods" to protein complexes involved in "docking" and "priming" vesicles to the active zone. Depending on their orientation, the "rods" define two synaptic vesicle-fusion paths: When parallel to the plasma membrane, the vesicles hemi-fuse anywhere ("randomly") in the active zone following the conventional path anticipated by the SNARE hypothesis. When perpendicular to the plasma membrane, the vesicles hemi-fuse at the base of sharp crooks, called "indentations," that are spaced 75-85 nm center-to-center, arranged in files and contained within gutters. They result from primary and secondary membrane curvatures that intersect at stationary inflection ("saddle") points. Computer simulations indicate that this novel vesicle-fusion path evokes neurotransmitter concentration domains on the post-synaptic spine that are wider, shallower, and that reach higher average concentrations than the more conventional vesicle fusion path. In the post-synaptic spine, large (∼9× ∼15 nm) rectangular particles at densities of 72±10/ µm2 (170-240/spine) match the envelopes of the homotetrameric GluR2 AMPA-sensitive receptor. While these putative receptors join clusters, called the "post-synaptic domains," the overwhelming majority of the rectangular particles formed bands in the "non-synaptic" plasma membrane of the spine. In conclusion, in the neuropil of the rat cerebral cortex, curvatures of the plasma membrane define a novel vesicle-fusion path that preconditions specific regions of the active zone for neurotransmitter release. We hypothesize that a change in the hybridization of the R-SNARE synaptobrevin

  9. Cholinergic enhancement increases regional cerebral blood flow to the posterior cingulate cortex in mild Alzheimer's disease.

    Science.gov (United States)

    Iizuka, Tomomichi; Kameyama, Masashi

    2017-06-01

    The brain region that shows reductions in regional cerebral blood flow (rCBF) earliest is the posterior cingulate cortex (PCC), which is thought to have a relationship with cognitive function. We made a hypothesis that the PCC hypoperfusion is a result of cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase inhibitor. We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex using perfusion single-photon emission computed tomography (SPECT), statistical analysis and region of interest analysis, prospectively. We allocated 36 patients with mild AD to either the responder or non-responder groups based on changes in Mini-Mental State Examination scores. The patients were followed up for 18 months. The PCC rCBF significantly increased in responders after 6 months of donepezil therapy. Statistical maps at baseline showed a typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at 6 months in responders. Changes in Mini-Mental State Examination scores and the AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders. Cholinergic enhancement restored PCC rCBF under the three conditions of mild AD, responders and short follow-up interval, and that increase correlated with improved cognitive function. These findings support our hypothesis that PCC rCBF reflects cholinergic function in AD patients. Geriatr Gerontol Int 2017; 17: 951-958. © 2016 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

  10. Effects of microgravity on muscle and cerebral cortex: a suggested interaction

    Science.gov (United States)

    D'Amelio, F.; Fox, R. A.; Wu, L. C.; Daunton, N. G.; Corcoran, M. L.

    The ``slow'' antigravity muscle adductor longus was studied in rats after 14 days of spaceflight (SF). The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light and electron microscopy revealed myofiber atrophy, segmental necrosis and regenerative myofibers. Regenerative myofibers were N-CAM immunoreactive (N-CAM-IR). The neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles, degenerative changes, vacant axonal spaces and changes suggestive of axonal sprouting. No alterations of muscle spindles was seen either by light or electron microscopy. These observations suggest that muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight. In a separate study, GABA immunoreactivity (GABA-IR) was evaluated at the level of the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension (``simulated'' microgravity). A reduction in number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-IR terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system after spaceflight and hindlimb suspension it is suggested that after limb unloading there are alterations of afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the changes observed in GABA immunoreactivity of cells and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

  11. Asymmetric activation of the anterior cerebral cortex in recipients of IRECA: Preliminary evidence for the energetic effects of an intention-based biofield treatment modality on human neurophysiology

    NARCIS (Netherlands)

    Pike, C.; Vernon, D.; Hald, L.A.

    2014-01-01

    Neurophysiologic studies of mindfulness link the health benefits of meditation to activation of the left-anterior cerebral cortex. The similarity and functional importance of intention and attentional stance in meditative and biofield therapeutic practices suggest that modulation of recipient

  12. Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats.

    Science.gov (United States)

    Harper, S L; Bohlen, H G

    1984-01-01

    The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2 = 40-45 mm Hg, PCO2 = 40-45 mm Hg, pH = 7.35-7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)-order arterioles were significantly (p less than 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p less than 0.05) larger in SHR compared to WKY. Only 1A and 4A has significantly (p less than 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10(-4) M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p greater than 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70-150 mm Hg and 100-200 mm Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p less than 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by

  13. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

    Directory of Open Access Journals (Sweden)

    Torres I.L.S.

    2001-01-01

    Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  14. Cognitive Control Processes and Functional Cerebral Asymmetries: Association with Variation in the Handedness-Associated Gene LRRTM1.

    Science.gov (United States)

    Beste, Christian; Arning, Larissa; Gerding, Wanda M; Epplen, Jörg T; Mertins, Alexandra; Röder, Melanie C; Bless, Josef J; Hugdahl, Kenneth; Westerhausen, René; Güntürkün, Onur; Ocklenburg, Sebastian

    2017-03-21

    Cognitive control processes play an essential role not only in controlling actions but also in guiding attentional selection processes. Interestingly, these processes are strongly affected by organizational principles of the cerebral cortex and related functional asymmetries, but the neurobiological foundations are elusive. We ask whether neurobiological mechanisms that affect functional cerebral asymmetries will also modulate effects of top-down control processes on functional cerebral asymmetries. To this end, we examined potential effects of the imprinted gene leucine-rich repeat transmembrane neuronal 1 (LRRTM1) on attentional biasing processes in a forced attention dichotic listening task in 983 healthy adult participants of Caucasian descent using the "iDichotic smartphone app." The results show that functional cerebral asymmetries in the language domain are associated with the rs6733871 LRRTM1 polymorphism when cognitive control and top-down attentional mechanisms modulate processes in bottom-up attentional selection processes that are dependent on functional cerebral asymmetries. There is no evidence for an effect of LRRTM1 on functional cerebral asymmetries in the language domain unrelated to cognitive control processes. The results suggest that cognitive control processes are an important factor to consider when being interested in the molecular genetic basis of functional cerebral architecture.

  15. Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

    Directory of Open Access Journals (Sweden)

    Geissy LL Araújo

    2014-03-01

    Full Text Available The morphogen Sonic Hedgehog (SHH plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

  16. Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral cortex by triazolobenzodiazepines

    Energy Technology Data Exchange (ETDEWEB)

    Obata, T.; Yamamura, H.I.

    1988-01-01

    The effects of triazolobenzodiazepines of GABA-stimulated /sup 36/Cl/sup -/ uptake by membrane vesicles from rat cerebral cortex were examined. Triazolam and alprazolam showed a significant enhancement of GABA-stimulated /sup 36/Cl/sup -/ uptake at 0.01-10 uM. On the other hand, adinazolam showed a small enhancement at 0.1-1 uM followed by a significant inhibition of GABA-stimulated /sup 36/Cl/sup -/ uptake at 100 uM. The enhancement of GABA-stimulated /sup 36/Cl/sup -/ uptake by 1 uM alprazolam was antagonized by Ro15-1788, a benzodiazepine antagonist, but the inhibition of this response by 30 uM adinazolam was not antagonized by Ro15-1788. These results indicate that triazolobenzodiazepines enhanced GABA-stimulated /sup 36/Cl/sup -/ uptake through benzodiazepine receptors. High concentrations of adinazolam inhibit GABA-stimulated /sup 36/Cl/sup -/ uptake which may be due to the direct blockade of GABA-gated chloride channel. 23 references, 4 figures.

  17. Analysis of Gene Expression Profiles in the Human Brain Stem, Cerebellum and Cerebral Cortex.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available The human brain is one of the most mysterious tissues in the body. Our knowledge of the human brain is limited due to the complexity of its structure and the microscopic nature of connections between brain regions and other tissues in the body. In this study, we analyzed the gene expression profiles of three brain regions-the brain stem, cerebellum and cerebral cortex-to identify genes that are differentially expressed among these different brain regions in humans and to obtain a list of robust, region-specific, differentially expressed genes by comparing the expression signatures from different individuals. Feature selection methods, specifically minimum redundancy maximum relevance and incremental feature selection, were employed to analyze the gene expression profiles. Sequential minimal optimization, a machine-learning algorithm, was employed to examine the utility of selected genes. We also performed a literature search, and we discuss the experimental evidence for the important physiological functions of several highly ranked genes, including NR2E1, DAO, and LRRC7, and we give our analyses on a gene (TFAP2B that have not been investigated or experimentally validated. As a whole, the results of our study will improve our ability to predict and understand genes related to brain regionalization and function.

  18. Human Cerebral Cortex Cajal-Retzius Neuron: Development, Structure and Function. A Golgi Study

    Directory of Open Access Journals (Sweden)

    Miguel eMarín-Padilla

    2015-02-01

    Full Text Available The development, morphology and possible functional activity of the Cajal-Retzius cell of the developing human cerebral cortex have been explored herein. The C-RC, of extracortical origin, is the essential neuron of the neocortex first lamina. It receives inputs from subcortical afferent fibers that reach the first lamina early in development. Although the origin and function of these original afferent fibers remain unknown, they target the first lamina sole neuron: the C-RC. The neuron’ orchestrates the arrival, size and stratification of all pyramidal neurons (from ependymal origin of the neocortex gray matter. Its axonic terminals spread radially and horizontally throughout the entire first lamina establishing contacts with the dendritic terminals of all gray matter pyramidal cells regardless of size, location and/or eventual functional roles. While the neuron axonic terminals spread radially and horizontally throughout the first lamina, the neuron’ bodies undergoes progressive developmental dilution and locating any of them in the adult brain become quite difficult. The neuron bodies are probably retained in the older regions of the developing neocortex while their axonic collaterals will spread throughout its more recent ones that, eventually, will represent the great majority of the brain surface. This will explain their bodies progressive dilution in the developing neocortex and, later, in the adult brain. Although quite difficult to locate the body of any of them, they have been described in the adult brain.

  19. Cellular and synaptic localization of EAAT2a in human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Marcello eMelone

    2011-01-01

    Full Text Available We used light and electron microscopic immunocytochemical techniques to analyze the distribution, cellular and synaptic localization of EAAT2, the main glutamate transporter, in normal human neocortex. EAAT2a immunoreactivity was in all layers and consisted of small neuropilar puncta and rare cells. In white matter EAAT2a+ cells were numerous. Electron microscopic studies showed that in gray matter ∼77% of immunoreactive elements were astrocytic processes, ∼14% axon terminals, ∼2.8% dendrites, whereas ∼5% were unidentifiable. In white matter, ∼81% were astrocytic processes, ∼17% were myelinated axons and ∼2.0% were unidentified. EAAT2a immunoreactivity was never in microglial cells and oligodendrocytes. Pre-embedding electron microscopy showed that ∼67% of EAAT2a expressed at (or in the vicinity of asymmetric synapses was in astrocytes, ∼17% in axon terminals, while ∼13% was both in astrocytes and in axons. Post-embeddeding electron microscopy studies showed that in astrocytic processes contacting asymmetric synapses and in axon terminals, gold particle density was ∼25.1 and ∼2.8 particles/µm2, respectively, and was concentrated in a membrane region extending for ∼300 nm from the active zone edge. Besides representing the first detailed description of EAAT2a in human cerebral cortex, these findings may contribute to understanding its role in the pathophysiology of neuropsychiatric diseases.

  20. Activity-Dependent Callosal Axon Projections in Neonatal Mouse Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tagawa

    2012-01-01

    Full Text Available Callosal axon projections are among the major long-range axonal projections in the mammalian brain. They are formed during the prenatal and early postnatal periods in the mouse, and their development relies on both activity-independent and -dependent mechanisms. In this paper, we review recent findings about the roles of neuronal activity in callosal axon projections. In addition to the well-documented role of sensory-driven neuronal activity, recent studies using in utero electroporation demonstrated an essential role of spontaneous neuronal activity generated in neonatal cortical circuits. Both presynaptic and postsynaptic neuronal activities are critically involved in the axon development. Studies have begun to reveal intracellular signaling pathway which works downstream of neuronal activity. We also review several distinct patterns of neuronal activity observed in the developing cerebral cortex, which might play roles in activity-dependent circuit construction. Such neuronal activity during the neonatal period can be disrupted by genetic factors, such as mutations in ion channels. It has been speculated that abnormal activity caused by such factors may affect activity-dependent circuit construction, leading to some developmental disorders. We discuss a possibility that genetic mutation in ion channels may impair callosal axon projections through an activity-dependent mechanism.

  1. Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae).

    Science.gov (United States)

    Hof, Patrick R; Van der Gucht, Estel

    2007-01-01

    Cetaceans diverged from terrestrial mammals between 50 and 60 million years ago and acquired, during their adaptation to a fully aquatic milieu, many derived features, including echolocation (in odontocetes), remarkable auditory and communicative abilities, as well as a complex social organization. Whereas brain structure has been documented in detail in some odontocetes, few reports exist on its organization in mysticetes. We studied the cerebral cortex of the humpback whale (Megaptera novaeangliae) in comparison to another balaenopterid, the fin whale, and representative odontocetes. We observed several differences between Megaptera and odontocetes, such as a highly clustered organization of layer II over the occipital and inferotemporal neocortex, whereas such pattern is restricted to the ventral insula in odontocetes. A striking observation in Megaptera was the presence in layer V of the anterior cingulate, anterior insular, and frontopolar cortices of large spindle cells, similar in morphology and distribution to those described in hominids, suggesting a case of parallel evolution. They were also observed in the fin whale and the largest odontocetes, but not in species with smaller brains or body size. The hippocampal formation, unremarkable in odontocetes, is further diminutive in Megaptera, contrasting with terrestrial mammals. As in odontocetes, clear cytoarchitectural patterns exist in the neocortex of Megaptera, making it possible to define many cortical domains. These observations demonstrate that Megaptera differs from Odontoceti in certain aspects of cortical cytoarchitecture and may provide a neuromorphologic basis for functional and behavioral differences between the suborders as well as a reflection of their divergent evolution. c 2006 Wiley-Liss, Inc.

  2. Manatee cerebral cortex: cytoarchitecture of the frontal region in Trichechus manatus latirostris.

    Science.gov (United States)

    Reep, R L; Johnson, J I; Switzer, R C; Welker, W I

    1989-01-01

    Members of the order Sirenia are unique among mammals in being the only totally aquatic herbivores. They display correspondingly specialized physiological, behavioral and anatomical features. There have been few reports concerning sirenian neuroanatomy, and most of these have consisted of gross anatomical observations. Our interest in Sirenia stems from the desire to understand neuroanatomical specializations in the context of behavior and the effort to elucidate trends in mammalian brain evolution. The architecture of frontal regions of cerebral cortex was investigated in several brains of the Florida manatee, Trichechus manatus latirostris. Through observation of sections stained for Nissl substance or myelinated fibers, several distinct cortical areas were identified on the basis of laminar organization. These range from areas with poorly defined laminae to those having 6 well-defined layers, some of which exhibit sublayers. Two cortical areas exhibit pronounced cell clusters in layer VI, and these stain positively for acetylcholinesterase and cytochrome oxidase. We hypothesize that these clusters may be involved in perioral tactile bristle function. Certain of our findings are consistent with previous observations in the literature on the brains of dugongs. On the basis of their lamination patterns, these frontal cortical areas appear to be organized into concentric zones of allocortex, mesocortex and isocortex.

  3. Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

    DEFF Research Database (Denmark)

    Golonzhka, Olga; Nord, Alex; Tang, Paul L F

    2015-01-01

    molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex....... Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate....

  4. Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size.

    Science.gov (United States)

    Ali, Farhan; Meier, Rudolf

    2008-11-01

    The rapid increase of brain size is a key event in human evolution. Abnormal spindle-like microcephaly associated (ASPM) is discussed as a major candidate gene for explaining the exceptionally large brain in humans but ASPM's role remains controversial. Here we use codon-specific models and a comparative approach to test this candidate gene that was initially identified in Homo-chimp comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at 16 amino acid sites occurred in 9 primate lineages with major changes in relative cerebral cortex size. However, ASPM's evolution is not correlated with major changes in relative whole-brain or cerebellum sizes. Our results suggest that a single candidate gene such as ASPM can influence a specific component of the brain across large clades through changes in a few amino acid sites. We furthermore illustrate the power of using continuous phenotypic variability across primates to rigorously test candidate genes that have been implicated in the evolution of key human traits.

  5. Neurodynamics of the prefrontal cortex during conditional visuomotor associations.

    Science.gov (United States)

    Loh, Marco; Pasupathy, Anitha; Miller, Earl K; Deco, Gustavo

    2008-03-01

    The prefrontal cortex is believed to be important for cognitive control, working memory, and learning. It is known to play an important role in the learning and execution of conditional visuomotor associations, a cognitive task in which stimuli have to be associated with actions by trial-and-error learning. In our modeling study, we sought to integrate several hypotheses on the function of the prefrontal cortex using a computational model, and compare the results to experimental data. We constructed a module of prefrontal cortex neurons exposed to two different inputs, which we envision to originate from the inferotemporal cortex and the basal ganglia. We found that working memory properties do not describe the dominant dynamics in the prefrontal cortex, but the activation seems to be transient, probably progressing along a pathway from sensory to motor areas. During the presentation of the cue, the dynamics of the prefrontal cortex is bistable, yielding a distinct activation for correct and error trails. We find that a linear change in network parameters relates to the changes in neural activity in consecutive correct trials during learning, which is important evidence for the underlying learning mechanisms.

  6. Relationship of angiogenesis and microglial activation to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy.

    Science.gov (United States)

    Sakurai, Masashi; Morita, Takehito; Takeuchi, Takashi; Shimada, Akinori

    2013-05-01

    microglial activation corresponded with seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Microglial activation induced by vascular endothelial growth factor and associated proinflammatory cytokine production may accelerate seizure-induced neuronal death in dogs with epilepsy.

  7. Association of Lead Levels and Cerebral Palsy

    OpenAIRE

    Neha Bansal MD; Anju Aggarwal MD, FIAP, MNAMS; M. M. A. Faridi MD, FIAP, MNAMS; Tusha Sharma PhD; B. D. Baneerjee PhD

    2017-01-01

    Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead leve...

  8. Thermogenesis elicited by skin cooling in anaesthetized rats: lack of contribution of the cerebral cortex

    Science.gov (United States)

    Osaka, Toshimasa

    2004-01-01

    Non-noxious cooling stimuli were delivered to the shaved back of urethane-chloralose-anaesthetized, artificially ventilated rats using a plastic bag containing water at 24–40°C. Cooling of the skin by 2–6°C increased the rate of whole body oxygen consumption (V̇O2) and triggered electromyographic (EMG) activity recorded from the neck or femoral muscles. The cooling-induced V̇O2 responses did not depend on core (colonic) temperature and followed skin temperature in a graded manner. Pretreatment with the β-blocker propranolol (10 mg kg−1, i.v.) greatly attenuated the V̇O2 response but did not affect the EMG response. On the other hand, pretreatment with the muscle relaxant pancuronium bromide (2 mg kg−1, i.v.) affected the V̇O2 response very slightly but completely abolished the EMG activity. Accordingly, the cooling stimulus activated mainly non-shivering thermogenesis. Next, the contribution of the cerebral cortex to the cooling-induced thermogenesis was examined. Power spectral analysis of the electroencephalogram (EEG) showed that the cooling stimulus largely inhibited delta (0.5–3 Hz) waves, enhanced theta (3–8 Hz) waves, and slightly increased frequencies higher than 8 Hz. Pinching the hindpaw elicited changes in EEG similar to those elicited by skin cooling but did not increase the V̇O2. Therefore, there was no relationship between changes in the EEG and the magnitude of thermogenesis. Finally, skin cooling increased the V̇O2 of decorticated rats but did not increase that of decerebrated rats. The results suggest that the subcortical forebrain structure, but not cortical activation, is indispensable for non-shivering thermogenesis elicited by cooling stimulation of the skin. PMID:14578483

  9. Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia.

    Science.gov (United States)

    Lee, Ben H; Wen, Tong-Chun; Rogido, Marta; Sola, Augusto

    2007-01-01

    Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI). GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group. Nissl staining was performed on FCI or S-O P7 cortical samples. Cortical GR expression was increased by 65.2% at P7, 110.1% at P15, and 87.0% at P30, compared to P1. On P7, GR expression decreased in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI (p cortex after 6 h and in the non-ischemic cortex after 24 h of FCI. Thus, cortical GR may play important roles in normal brain development and neonatal brain injury responses.

  10. [Correlation of diffusion tensor imaging between the cerebral cortex and speech discrimination in presbycusis].

    Science.gov (United States)

    Peng, Lu; Yu, Shuilian; Chen, Ruichun; Jing, Yan; Liang, Jianping

    2015-09-01

    To investigate the relationship between pure-tone average (PTA), the fractional anisotropy (FA) of the auditory pathway, cognitive cortex and auditory cortex in presbycusis. Twenty-five elderly subjects with presbycusis were participated in the study. PTA, speech discrimination abilities were evaluated in each subject. Diffusion tensor imaging (DTI) was applied to access the FA of the IC, the superior frontal gyrus and the Heschl's gyrus. Compare the difference between two sides of the values of FA in the three areas. Bivariate correlation analysis was performed to evaluate the effects of PTA and FA of the inferior colliculus (IC), the superior frontal gyrus and the Heschl's gyrus on speech discrimination abilities. There were no significant differences between the left and right side of the inferior colliculus (P > 0.05). Higher FA values were recorded at the left side of the Heschl's gyrus and the superior frontal gyrus (P < 0.05). Both PTA and the FA of the superior frontal gyrus have a negative association with speech discrimination abilities (P < 0.01, P < 0.05), while the FA of the Heschl's gyrus has a positive association with speech discrimination abilities (P < 0.05). Our findings indicated that the speech discrimination abilities of the elderly is not only related to the peripheral auditory function, but also to the central auditory and cognitive function.

  11. [Effect of Reading a Book on a Tablet Computer on Cerebral Blood Flow in the Prefrontal Cortex].

    Science.gov (United States)

    Sugiura, Akihiro; Eto, Takuya; Kinoshita, Fumiya; Takada, Hiroki

    2018-01-01

    By measuring cerebral blood flow in the prefrontal cortex, we aimed to determine how reading a book on a tablet computer affects sleep. Seven students (7 men age range, 21-32 years) participated in this study. In a controlled illuminance environment, the subjects read a novel in printed form or on a tablet computer from any distance. As the subjects were reading, the cerebral blood flow in their prefrontal cortex was measured by near-infrared spectroscopy. The study protocol was as follows. 1) Subjects mentally counted a sequence of numbers for 30 s as a pretest to standardized thinking and then 2) read the novel for 10 min, using the printed book or tablet computer. In step 2), the use of the book or tablet computer was in a random sequence. Subjects rested between the two tasks. Significantly increased brain activity (increase in regional cerebral blood flow) was observed following reading a novel on a tablet computer compared with that after reading a printed book. Furthermore, the region around Broca's area was more active when reading on a tablet computer than when reading a printed book. Considering the results of this study and previous studies on physiological characteristics during nonrapid eye movement sleep, we concluded that reading a book on a tablet computer before the onset of sleep leads to the potential inhibition of sound sleep through mechanisms other than the suppression of melatonin secretion.

  12. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    Science.gov (United States)

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  13. Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Christophe Heinrich

    2014-12-01

    Full Text Available The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

  14. [Changes of endoplasmic reticulum stress- and apoptosis-related factors in rat cerebral cortex following controlled hypotension].

    Science.gov (United States)

    Zhang, Jianxing; Li, Hongying; Zhou, Guobin; Wang, Yan

    2014-12-01

    To investigate the changes of endoplasmic reticulum stress (ERS)- and apoptosis-related factors in rat cerebral cortex following controlled hypotension. Twenty-four healthy male SD rats were randomly divided into 4 equal groups, including a sham hypotension group (group A) and 3 hypotension groups with the mean arterial pressure maintained for 60 min at 70 mmHg (group B), 50 mmHg (group) and 30 mmHg (group D) with sodium nitroprusside and esmolol. All the rats received an equal volume of fluid infusion. Twelve hours after controlled hypotension, the rats were sacrificed to examine the protein expressions of Bax, Bcl-2, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 in the cortex with Western blotting. GRP78 mRNA expression was measured by RT-PCR, and the cell apoptosis was evaluated by TUNEL staining. Compared with those in group A, GRP78 mRNA and protein expressions of GRP78, CHOP, caspase-12 related with ERS increased significantly in groups C and D (P0.05). Apoptotic cells and Bax expression increased and Bcl-2 expression decreased significantly in groups C and D (P0.05); such changes were more prominent in group D than in group C (Pcontrolled hypotension (70 mmHg) does not induce neuronal injury in rat cerebral cortex, but severe hypertension (lower than 50 mmHg) can cause neuronal ERS and apoptosis.

  15. Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure.

    Science.gov (United States)

    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hak Rim

    2017-03-01

    With the explosive increase in exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones, public concerns have grown over the last few decades with regard to the potential effects of EMF exposure on the nervous system in the brain. Many researchers have suggested that RF-EMFs can effect diverse neuronal alterations in the brain, thereby affecting neuronal functions as well as behavior. Previously, we showed that long-term exposure to 835 MHz RF-EMF induces autophagy in the mice brain. In this study, we explore whether short-term exposure to RF-EMF leads to the autophagy pathway in the cerebral cortex and brainstem at 835 MHz with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Increased levels of autophagy genes and proteins such as LC3B-II and Beclin1 were demonstrated and the accumulation of autophagosomes and autolysosomes was observed in cortical neurons whereas apoptosis pathways were up-regulated in the brainstem but not in the cortex following 4 weeks of RF exposure. Taken together, the present study indicates that monthly exposure to RF-EMF induces autophagy in the cerebral cortex and suggests that autophagic degradation in cortical neurons against a stress of 835 MHz RF during 4 weeks could correspond to adaptation to the RF stress environment. However, activation of apoptosis rather than autophagy in the brainstem is suggesting the differential responses to the RF-EMF stresses in the brain system.

  16. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

    Directory of Open Access Journals (Sweden)

    Sérgio Gomes da Silva

    Full Text Available Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task. Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation and associative (spatial learning mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning and increases BDNF levels and cell numbers in the hippocampal formation of offspring.

  17. Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring

    Directory of Open Access Journals (Sweden)

    Tianliang Zhang

    2018-01-01

    Full Text Available Air pollution is a serious environmental health problem closely related to the occurrence of central nervous system diseases. Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5 during pregnancy may affect the growth and development of infants. The present study was to investigate the effects of maternal exposure to PM2.5 during pregnancy on brain development in mice offspring. Pregnant mice were randomly divided into experimental groups of low-, medium-, or high-dosages of PM2.5, a mock-treated group which was treated with the same amount of phosphate buffer solution (PBS, and acontrol group which was untreated. The ethology of offspring mice on postnatal days 1, 7, 14, 21, and 30, along with neuronal development and apoptosis in the cerebral cortex were investigated. Compared with the control, neuronal mitochondrial cristae fracture, changed autophagy characteristics, significantly increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL positive cell rate, and mRNA levels of apoptosis-related caspase-8 and caspase-9 were found in cerebral cortex of mice offspring from the treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased. Treatment groups also demonstrated enhanced protein expressions of apoptosis-related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with declined proliferating cell nuclear antigen (PCNA, Bcl-2, and ratio of Bcl-2 to Bax. Open field experiments and tail suspension experiments showed that exposure to high dosage of PM2.5 resulted in decreased spontaneous activities but increased static accumulation time in mice offspring, indicating anxiety, depression, and social behavioral changes. Our results suggested that maternal exposure to PM2.5 during pregnancy might interfere with cerebral cortex development in mice offspring by affecting cell apoptosis.

  18. Distinction of neurons, glia and endothelial cells in the cerebral cortex: an algorithm based on cytological features

    Directory of Open Access Journals (Sweden)

    Miguel Ángel García-Cabezas

    2016-11-01

    Full Text Available The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic, and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease.

  19. Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard

    2010-01-01

    two different sets of interneurons. Our data imply that for a given cortical area the amplitude of vascular signals will depend critically on the type of input and hence on the type of neurons activated. In the second study I investigated the effect of cortical spreading depression (CSD) on the evoked...... Laser-Doppler Flowmetry for measurements of cerebral blood flow, glass microelectrodes for recording of synaptic activity – local field potentials – and ongoing cortical electrical activity and a Clark type electrode for measurements of tissue partial pressure of oxygen (tpO2). Offline calculations......As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...

  20. Hypoperfusion of the Cerebellum and Aging Effects on Cerebral Cortex Blood Flow in Abstinent Alcoholics: A SPECT Study

    Science.gov (United States)

    Harris, Gordon J.; Oscar-Berman, Marlene; Gansler, A.; Streeter, Chris; Lewis, Robert F.; Ahmed, Iqbal; Achong, Dwight

    2014-01-01

    Background This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. Methods The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). Results In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics and nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. Conclusions The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline. PMID:10443989

  1. Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard

    2010-01-01

    As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...... parameters of the whisker/infraorbital nerve etwork (IO) targeting the same cortical area. We tested the hypothesis that the relation between increases in CBF and CMRO2 evoked by stimulation and synaptic activity differed for the two activated networks and that activation of two distinct networks activate...

  2. [Structural and functional reorganization of the interneuronal contacts of the cerebral cortex after a single convulsive paroxysm].

    Science.gov (United States)

    Savchenko, Iu N; Ereniev, S I; Semchenko, V V; Stepanov, S S

    1987-01-01

    Using the technique of contrasting the cerebral tissue with phosphotungstic acid, the authors studied the structural and functional status of interneuronal contacts of the molecular layer of the sensomotor cortex in the brain of Krushinsky-Molodkina rats following convulsive sound stimulation and the subsequent audiogenic convulsive paroxysm. Marked reduction in the general number of synapses 4 h after the attack was attended by transformation of some flat functionally mature contacts into concave ones, which reflects the activation of the synaptic pool. The relative levels of concave and flat mature contacts returned to the initial level 8 to 24 h later.

  3. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Li LIU

    2013-03-01

    Full Text Available Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results  Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions  Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

  4. Stroke associated with left atrial mass: Association of cerebral aneurysm with left atrial myxoma!

    Directory of Open Access Journals (Sweden)

    Shashi Srivastava

    2014-01-01

    Full Text Available Association of LA myxoma with cerebral aneurysm is rare. We describe a patient who had LA mass and cerebral aneurysm and developed stroke. The patient underwent clipping of the cerebral aneurysm. We discuss the pathology of the association and the anesthetic management.

  5. Evolutionary appearance of von Economo's neurons in the mammalian cerebral cortex.

    Science.gov (United States)

    Cauda, Franco; Geminiani, Giuliano Carlo; Vercelli, Alessandro

    2014-01-01

    von Economo's neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the "social brain." VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the "global Workspace" architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental

  6. Evolutionary appearance of von Economo’s neurons in the mammalian cerebral cortex

    Science.gov (United States)

    Cauda, Franco; Geminiani, Giuliano Carlo; Vercelli, Alessandro

    2014-01-01

    von Economo’s neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the “social brain.” VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the “global Workspace” architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and

  7. Evolutionary appearance of Von Economo’s Neurons in the mammalian cerebral cortex

    Directory of Open Access Journals (Sweden)

    Franco eCauda

    2014-03-01

    Full Text Available Von Economo’s neurons (VENs are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months.VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the social brain. VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain.However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the global Workspace architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication between salience-related insular and cingulate and other widely separated brain areas.Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the fMRI data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental investigatio

  8. Association of Lead Levels and Cerebral Palsy.

    Science.gov (United States)

    Bansal, Neha; Aggarwal, Anju; Faridi, M M A; Sharma, Tusha; Baneerjee, B D

    2017-01-01

    Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods:Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P cerebral palsy, 19 (55.88%) children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children.

  9. Association of Lead Levels and Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Neha Bansal MD

    2017-03-01

    Full Text Available Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer. Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001. Among children with cerebral palsy, 19 (55.88% children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029. No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children.

  10. Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects

    Directory of Open Access Journals (Sweden)

    Patrick Schiffler

    2017-07-01

    Full Text Available The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner.

  11. Systemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid content of mouse cerebral cortex.

    Science.gov (United States)

    Heyes, M P; Quearry, B J; Markey, S P

    1989-07-03

    Systemic infections and injection of endotoxin are known to increase L-tryptophan release from skeletal muscle and increase systemic L-tryptophan catabolism through the kynurenine pathway. To investigate the effects of systemically administered endotoxin on brain L-tryptophan metabolites. C57BL6/6NCR mice were given an intraperitoneal injection of 10 micrograms of lipopolysaccharide from Salmonella abortus equii and samples of serum and cerebral cortex collected. After 9 h, serum L-tryptophan concentration was decreased by 51%. At 9 h and 24 h, increases in L-tryptophan metabolites in cerebral cortex were: L-tryptophan, 42% and 39%; 5-hydroxyindoleacetic acid, 38% and 67%; 3-hydroxykynurenine, 235% and 381%; and quinolinic acid, 76% and 306%. Cortical quinolinic acid concentration was still elevated at 48 h (88%) and 72 h (79%) after lipopolysaccharide. No significant changes in cortical serotonin concentrations were found at the time points examined. When L-tryptophan (0.37 mmol/kg) was administered systemically to either normal or lipopolysaccharide-treated mice, increases in cortical L-tryptophan, serotonin, 5-hydroxyindoleacetic acid and 3-hydroxykynurenine concentrations were largest in mice treated with both lipopolysaccharide and L-tryptophan. These results suggest that disturbances in L-tryptophan metabolism that follow systemic endotoxin administration extend to the central nervous system. The consequences of these changes in L-tryptophan metabolites remain to be determined.

  12. Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS.

    Science.gov (United States)

    Iacovitti, L; Lee, J; Joh, T H; Reis, D J

    1987-04-01

    In vivo, neurons of the cerebral cortex of rat embryos did not stain with antibodies to the catecholamine (CA) biosynthetic enzyme tyrosine hydroxylase (TH) even when examined using a highly sensitive technique for radioimmunocytochemistry. However, when embryonic day (E) 13 cortex was grown 1 d in culture, several thousand cells expressed immunoreactive and catalytically active TH. All TH cells simultaneously labeled with the neuronal enzyme, neuronal specific enolase, indicating that the TH was exclusively localized in neurons. Moreover, all TH neurons were postmitotic since they did not incorporate 3H-thymidine. With time in culture, the number of TH cells selectively declined from nearly 3000 cells at 2 d to several cells at 14 d. Similarly, the number of neurons competent to express TH in culture declined with advancing age of the donor embryo. Thus, by E18, very few cortical neurons had the capacity to express TH. We conclude that during a critical period of development, postmitotic cerebral cortical neurons can express catecholamine traits in vitro but not in vivo. Thus, the neurotransmitter phenotype of certain classes of central neurons is not fixed but can be influenced by epigenetic factors found in their environment, thereby providing evidence of phenotypic plasticity in the central nervous system (CNS).

  13. Cross-sectional Associations of Fatigue with Cerebral β-Amyloid in Older Adults at Risk of Dementia

    Directory of Open Access Journals (Sweden)

    Claudie Hooper

    2017-11-01

    Full Text Available Fatigue is a common symptom in the elderly and has also been associated with impaired cognition in older adults. Hence, we sought to explore the cross-sectional relationship between fatigue and cerebral β-amyloid (Aβ in 269 elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial. Standard uptake value ratios (SUVRs were generated by [18F] florbetapir positron emission tomography (PET using the cerebellum as a reference. Cortical-to-cerebellar SUVRs (cortical-SUVRs were obtained using the mean signal from the frontal cortex, temporal cortex, parietal cortex, precuneus, anterior cingulate, and posterior cingulate. Other brain regions independently assessed were the anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex. Fatigue was defined according to two questions retrieved from the Center for Epidemiological Studies-Depression scale. Chronic fatigue was defined as meeting fatigue criteria at two consecutive clinical visits 6 months apart between study baseline and 1 year (visits were performed at baseline, 6 months and 1 year then annually. Cross-sectional associations between fatigue variables and cerebral Aβ were explored using fully adjusted multiple linear regression models. We found no statistically significant cross-sectional associations between fatigue assessed at the clinical visit closest to PET and Aβ in any brain region. Similarly, chronic fatigue was not significantly associated with Aβ load. Sensitivity analysis in subjects with a Clinical Dementia Rating of 0.5 showed that fatigue reported at the clinical visit closest to PET was, however, weakly associated with increased Aβ in the hippocampus (B-coefficient: 0.07, 95% CI: 0.01, 0.12, p = 0.016. These preliminary results suggest that fatigue might be

  14. The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

    Directory of Open Access Journals (Sweden)

    Mariella eErrede

    2014-10-01

    Full Text Available This study was conducted on human developing brain by laser confocal and transmission electron microscopy to make a detailed analysis of important features of blood-brain barrier microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The blood-brain barrier status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration and before cortex lamination, with blood-brain barrier-endothelial cell markers, namely tight junction proteins (occludin and claudin-5 and influx and efflux transporters (Glut-1 and P-glycoprotein, the latter supporting evidence for functional effectiveness of the fetal blood-brain barrier. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analysed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43 were utilized as markers of radial glia cells, CD105 (endoglin as a marker of angiogenically activated endothelial cells, and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial fibres in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical vessel-specific RG fibre swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of radial glial varicosities reveals colocalization of CXCL12 with connexin Cx43, which is possibly implicated in vessel-specific chemokine signalling.

  15. Multi-Regional Adaptation in Human Auditory Association Cortex

    Directory of Open Access Journals (Sweden)

    Urszula Malinowska

    2017-05-01

    Full Text Available In auditory cortex, neural responses decrease with stimulus repetition, known as adaptation. Adaptation is thought to facilitate detection of novel sounds and improve perception in noisy environments. Although it is well established that adaptation occurs in primary auditory cortex, it is not known whether adaptation also occurs in higher auditory areas involved in processing complex sounds, such as speech. Resolving this issue is important for understanding the neural bases of adaptation and to avoid potential post-operative deficits after temporal lobe surgery for treatment of focal epilepsy. Intracranial electrocorticographic recordings were acquired simultaneously from electrodes implanted in primary and association auditory areas of the right (non-dominant temporal lobe in a patient with complex partial seizures originating from the inferior parietal lobe. Simple and complex sounds were presented in a passive oddball paradigm. We measured changes in single-trial high-gamma power (70–150 Hz and in regional and inter-regional network-level activity indexed by cross-frequency coupling. Repetitive tones elicited the greatest adaptation and corresponding increases in cross-frequency coupling in primary auditory cortex. Conversely, auditory association cortex showed stronger adaptation for complex sounds, including speech. This first report of multi-regional adaptation in human auditory cortex highlights the role of the non-dominant temporal lobe in suppressing neural responses to repetitive background sounds (noise. These results underscore the clinical utility of functional mapping to avoid potential post-operative deficits including increased listening difficulties in noisy, real-world environments.

  16. Increased 20-HETE synthesis explains reduced cerebral blood flow but not impaired neurovascular coupling after cortical spreading depression in rat cerebral cortex

    DEFF Research Database (Denmark)

    Fordsmann, Jonas Christoffer; ko, Rebecca; Choi, Hyun B

    2013-01-01

    Cortical spreading depression (CSD) is associated with release of arachidonic acid (AA), impaired neurovascular coupling, and reduced cerebral blood flow (CBF), caused by cortical vasoconstriction. We tested the hypothesis that the released AA is metabolized by the cytochrome P450 enzyme to produ...

  17. Microvascular Adaptation in the Cerebral Cortex of Adult Spontaneously Hypertensive Rats

    National Research Council Canada - National Science Library

    HARPER, SCOT L; BOHLEN, H GLENN

    1984-01-01

    The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established...

  18. [Neonatal ultrasonographic cerebral findings: association with risk factor for cerebral palsy].

    Science.gov (United States)

    Staneva, K N; Hartmann, S; Uhlemann, M; Dietze, H; Reschke, E; Koepcke, E; Sadenwasser, W; Külz, Th

    2002-01-01

    Is it possible to identify patients with cerebral palsy (CP) with postnatal ultrasound scan? Which risk factors are associated with an increased risk of CP?. The data of 37 children with CP, who were sonographically investigated during the first 24 hours of life were analyzed retrospectively. The data of 21 preterm infants with gestational age /= 33 wk and in 5/8 of the mature babies. The mature babies had prenatal brain atrophy or hypoxic-ischaemic cerebral lesions. Cytomegaly and encephalitis were detected in two babies. Immature babies >/= 33 wk showed prenatal porencephaly or encephalomalacia after asphyxia. Premature babies cystic periventricular leucomalacia (n=12) or cerebral haemorrhage (n=3); 3 babies had meningitis. Only two prematures cystic periventricular leucomalacia (OR 24,89; 95 % CI: 5,85 - 105,87), cerebral atrophy (OR 4,84; 95 % CI: 1,61 - 14,51), fetal hypoxia (CTG) - (OR 4,78; 95 % CI: 1,31 - 17,45), abruptio placentae (OR 4,32; 95 % CI: 1,16 - 16,13), anemia after birth (OR 18,13; 95 % CI: 1,97 - 166,43), abnormal neurological behavior at term (OR 14,00; 95 % CI: 3,29 - 59,55). Cerebral ultrasound scan after birth is a useful method detect for cerebral lesions in patients with CP-risks.

  19. Atypical cerebral listeriosis associated with Listeria innocua in a beef bull.

    Science.gov (United States)

    Rocha, Paulo Ricardo Dell'Armelina; Dalmasso, Alessandra; Grattarola, Carla; Casalone, Cristina; Del Piero, Fabio; Bottero, Maria Teresa; Capucchio, Maria Teresa

    2013-02-01

    Natural infections of cattle associated with Listeria innocua have not been reported. This report describes the first case of cerebral listeriosis in a bull due to Listeria innocua. The animal presented neurological signs characterized by weakness, incoordination and recumbency. Histopathologic evaluation of brain tissue revealed multifocal microabscesses, perivascular lymphocytic cuffing, vasculitis, oedema and haemorrhages. All lesions extended from the medulla oblongata to the basal nuclei/parietal cortex area. Indirect immunohistochemistry labelled for Listeria sp. in the brain tissue, but not for Listeria monocytogenes, neurotropic Flaviviruses, BVDV, bovine Herpesvirus 1, Chlamydophila spp. and Histophilus somni. PCR was negative for ovine herpesvirus. L. innocua was isolated from brainstem and identified by biochemical tests (Camp and beta-hemolysis negative). Subsequently, the species was confirmed by a duplex PCR and minisequencing assays. L. innocua should be histologically considered as a differential diagnosis of thrombotic meningoencephalitis, malignant catarrhal fever and cerebral listeriosis due to L. monocytogenes in cattle. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex.

    Science.gov (United States)

    Alexander, S P; Curtis, A R; Kendall, D A; Hill, S J

    1994-12-01

    1. A1 adenosine receptors were investigated by radioligand binding and functional studies in slices and particulate preparations from guinea-pig cerebral cortex. 2. Binding of the adenosine receptor antagonist radioligand, 8-cyclopentyl-[3H]-1,3-dipropylxanthine (DPCPX) to guinea-pig cerebral cortical membranes exhibited high density (1410 +/- 241 fmol mg-1 protein) and high affinity (Kd 3.8 +/- 0.3 nM). 3. [3H]-DPCPX binding to guinea-pig cerebral cortical membranes was displaced in a monophasic manner by adenosine receptor antagonists with the rank order of affinity (Ki values, nM): DPCPX (6) < xanthine amine congener (XAC, 153) < PD 115,199 (308). 4. Agonist displacement of [3H]-DPCPX binding was biphasic and exhibited the following rank order at the low affinity site (Ki values): 2-chloro-N6-cyclopentyl-adenosine (CCPA, 513 nM) = N6-R-phenylisopropyladenosine (R-PIA, 526 nM) = N6-cyclopentyladenosine (CPA, 532 nM) < 2-chloroadenosine (2CA, 3.2 microM) = 5'-N-ethylcarboxamidoadenosine (NECA, 4.6 microM) < N6-S-phenylisopropyladenosine (S-PIA, 19.9 microM). 5. In cerebral cortical slices, [3H]-DPCPX binding was displaced by antagonists and agonists in an apparently monophasic manner with the rank order of affinity (Ki values, nM): DPCPX (14) < XAC (45) < R-PIA (266) < PD 115,199 (666) < S-PIA (21000). 6. Cyclic AMP accumulation stimulated by 30 microM forskolin in guinea-pig cerebral cortical slices was inhibited by R-PIA, CCPA and CPA up to 1 microM in a concentration-dependent fashion with IC50 values of 14, 18, and 22 nM, respectively. All three analogues inhibited the forskolin response to a similar extent (82-93% inhibition). NECA, S-PTA and 2CA failed to inhibit the forskolin response, but rather enhanced the accumulation of cyclic AMP at concentrations of 100 nM or greater, presumably through activation of A2b adenosine receptors coupled to stimulation of cyclic AMP accumulation in guinea-pig cerebral cortical slices.7. The inhibition of forskolin

  1. F3/Contactin acts as a modulator of neurogenesis during cerebral cortex development.

    Science.gov (United States)

    Bizzoca, Antonella; Corsi, Patrizia; Polizzi, Angela; Pinto, Marco F; Xenaki, Dia; Furley, Andrew J W; Gennarini, Gianfranco

    2012-05-01

    The expression of the cell recognition molecule F3/Contactin (CNTN1) is generally associated with the functions of post-mitotic neurons. In the embryonic cortex, however, we find it expressed by proliferating ventricular zone (VZ) precursors. In contrast to previous findings in the developing cerebellum, F3/Contactin transgenic overexpression in the early cortical VZ promotes proliferation and expands the precursor pool at the expense of neurogenesis. At later stages, when F3/Contactin levels subside, however, neurogenesis resumes, suggesting that F3/Contactin expression in the VZ is inversely related to neurogenesis and plays a role in a feedback control mechanism, regulating the orderly progression of cortical development. The modified F3/Contactin profile therefore results in delayed corticogenesis, as judged by downregulation in upper and lower layer marker expression and by BrdU birth dating, indicating that, in this transgenic model, increased F3/Contactin levels counteract neuronal precursor commitment. These effects also occur in primary cultures and are reproduced by addition of an F3/Fc fusion protein to wild type cultures. Together, these data indicate a completely novel function for F3/Contactin. Parallel changes in the generation of the Notch Intracellular Domain and in the expression of the Hes-1 transcription factor indicate that activation of the Notch pathway plays a role in this phenotype, consistent with previous in vitro reports that F3/Contactin is a Notch1 ligand. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. [Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

    Science.gov (United States)

    Wang, Zhuo-Yu; Ma, Jia-Jia; Guan, Han-Yu; Tian, Yao; Ren, Xiu-Jun; Ma, Hui-Fang

    2017-04-25

    To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl3 solution (10 μL). Rats of the sham operation group were treated with the same procedures only without application of FeCl3 solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well as

  3. Neuronal correlate of visual associative long-term memory in the primate temporal cortex

    Science.gov (United States)

    Miyashita, Yasushi

    1988-10-01

    In human long-term memory, ideas and concepts become associated in the learning process1. No neuronal correlate for this cognitive function has so far been described, except that memory traces are thought to be localized in the cerebral cortex; the temporal lobe has been assigned as the site for visual experience because electric stimulation of this area results in imagery recall,2 and lesions produce deficits in visual recognition of objects3-9. We previously reported that in the anterior ventral temporal cortex of monkeys, individual neurons have a sustained activity that is highly selective for a few of the 100 coloured fractal patterns used in a visual working-memory task10. Here I report the development of this selectivity through repeated trials involving the working memory. The few patterns for which a neuron was conjointly selective were frequently related to each other through stimulus-stimulus association imposed during training. The results indicate that the selectivity acquired by these cells represents a neuronal correlate of the associative long-term memory of pictures.

  4. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-02-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  5. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-03-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  6. Effect of Intranasally Delivered rh-VEGF165 on Angiogenesis Following Cerebral Hypoxia-Ischemia in the Cerebral Cortex of Newborn Piglets

    Directory of Open Access Journals (Sweden)

    Amit Jain

    2017-11-01

    Full Text Available Background: Vascular endothelial growth factor (VEGF stimulates vascular genesis and angiogenesis. Cerebral Hypoxia-Ischemia (HI leads to the reduction of vasculature in the cerebral cortex of newborn piglets. Objective: The present study tests the hypothesis that post-hypoxia intranasal administration of recombinant human VEGF165 (rh-VEGF165 for 3 days increases the vascular density in the cerebral cortex of newborn piglets without promoting neovascularization. Design/Methods: Ventilated newborn piglets were divided into three groups (n = 5/group: normoxic (Nx, hypoxic-ischemic (HI, and HI treated with intranasal rh-VEGF165rh-VEGF165 (HI-VEGF. HI piglets were exposed to HI (0.05 FiO2 for 30 min. Recombinant h-VEGF165 (100 ng/kg was administered 15 min after HI and then once daily for 3 days. The animals were perfused transcardially and coronal brains sections were processed for Isolectin, Hoechst, and ki-67 cell proliferation marker staining. To assess the vascular density, 30–35 fields per animal section were manually counted using image J software. Results: The vascular density (vessels/mm2 was 42.0 ± 8.0 in the Nx group, 26.4 ± 4.8 (p < 0.05 vs. Nx in the HI group, and 46.0 ± 11.9 (p < 0.05 vs. HI in the HI-VEGF group. When stained for newly formed vessels, via Ki-67 staining, the vascular density was 5.4 ± 3.6 in the Nx group (p < 0.05 vs. HI, 10.2 ± 2.1 in the HI group, and 10.9 ± 2.9 in the HI-VEGF group (p = 0.72 vs. HI. HI resulted in a decrease in vascular density. Intranasal rh-VEGF165rh-VEGF165 resulted in the attenuation of the HI-induced decrease in vascular density. However, rh-VEGF165 did not result in the formation of new vascularity, as evident by ki-67 staining. Conclusions: Intranasal rh-VEGF165 may prevent the HI-induced decrease in the vascular density of the brain and could serve as a promising adjuvant therapy for hypoxic-ischemic encephalopathy (HIE.

  7. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats.

    Science.gov (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg -1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups.

  8. Wernicke's encephalopathy induced by total parenteral nutrition in patient with acute leukaemia: unusual involvement of caudate nuclei and cerebral cortex on MRI

    Energy Technology Data Exchange (ETDEWEB)

    D' Aprile, P.; Tarantino, A.; Carella, A. [Division of Neuroradiology, Policlinico, Univ. of Bari (Italy); Santoro, N. [Inst. of Paediatric Clinic I, Policlinico, University of Bari, Bari (Italy)

    2000-10-01

    We report a 13-year-old girl with leukaemia and Wernicke's encephalopathy induced by total parenteral nutrition. MRI showed unusual bilateral lesions of the caudate nuclei and cerebral cortex, as well as typical lesions surrounding the third ventricle and aqueduct. After intravenous thiamine, the patient improved, and the abnormalities on MRI disappeared. (orig.)

  9. Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study.

    Science.gov (United States)

    Sutoh, Chihiro; Koga, Yasuko; Kimura, Hiroshi; Kanahara, Nobuhisa; Numata, Noriko; Hirano, Yoshiyuki; Matsuzawa, Daisuke; Iyo, Masaomi; Nakazato, Michiko; Shimizu, Eiji

    2016-01-01

    Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  10. Exposure to brominated flame retardant PBDE-99 affects cytoskeletal protein expression in the neonatal mouse cerebral cortex

    DEFF Research Database (Denmark)

    Alm, Henrik; Kultima, Kim; Scholz, Birger

    2008-01-01

    Polybrominated diphenyl ethers (PBDEs) are environmental contaminants found in human and animal tissues worldwide. Neonatal exposure to the flame retardant 2,2', 4,4',5-pentabromodiphenyl ether (PBDE-99) disrupts normal brain development in mice, and results in disturbed spontaneous behavior....... Protein resolution was enhanced by sample pre-fractionation. In the cell model, we determined cell viability using the trypan blue exclusion assay, and apoptosis using immunocytochemical detection of cleaved caspase-3. We determined the identity of 111 differentially expressed proteins, 32 (29%) of which...... activity. These results indicate that the permanent neurological damage induced by PBDE-99 during the brain growth spurt involve detrimental effects on cytoskeletal regulation and neuronal maturation in the developing cerebral cortex....

  11. Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard

    2010-01-01

    As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...... two different sets of interneurons. Our data imply that for a given cortical area the amplitude of vascular signals will depend critically on the type of input and hence on the type of neurons activated. In the second study I investigated the effect of cortical spreading depression (CSD) on the evoked...... responses of synaptic activity (LFP), CBF, tpO2 and CMRO2 in the TC network. Also the impact on neurovascular and neurometabolic coupling were examined. Last but not least the influence of CSD on ongoing (baseline) CBF and CMRO2 was examined. The results demonstrate a long lasting effect of CSD on baseline...

  12. Intraoperative optical coherence tomography of the cerebral cortex using a 7 degree-of freedom robotic arm

    Science.gov (United States)

    Reyes Perez, Robnier; Jivraj, Jamil; Yang, Victor X. D.

    2017-02-01

    Optical Coherence Tomography (OCT) provides a high-resolution imaging technique with limited depth penetration. The current use of OCT is limited to relatively small areas of tissue for anatomical structure diagnosis or minimally invasive guided surgery. In this study, we propose to image a large area of the surface of the cerebral cortex. This experiment aims to evaluate the potential difficulties encountered when applying OCT imaging to large and irregular surface areas. The current state-of-the-art OCT imaging technology uses scanning systems with at most 3 degrees-of-freedom (DOF) to obtain a 3D image representation of the sample tissue. We propose the use of a 7 DOF industrial robotic arm to increase the scanning capabilities of our OCT. Such system will be capable of acquiring data from large samples of tissue that are too irregular for conventional methods. Advantages and disadvantages of our system are discussed.

  13. The role of α-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration.

    Science.gov (United States)

    Schmid, Marie-Theres; Weinandy, Franziska; Wilsch-Bräuninger, Michaela; Huttner, Wieland B; Cappello, Silvia; Götz, Magdalena

    2014-01-01

    During brain development, radial glial cells possess an apico-basal polarity and are coupled by adherens junctions (AJs) to an F-actin belt. To elucidate the role of the actin, we conditionally deleted the key component α-E-catenin in the developing cerebral cortex. Deletion at early stages resulted in severe disruption of tissue polarity due to uncoupling of AJs with the intracellular actin fibers leading to the formation of subcortical band heterotopia. Interestingly, this phenotype closely resembled the phenotype obtained by conditional RhoA deletion, both in regard to the macroscopic subcortical band heterotopia and the subcellular increase in G-actin/F-actin ratio. These data therefore together corroborate the role of the actin cytoskeleton and its anchoring to the AJs for neuronal migration disorders.

  14. The role of α-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration

    Directory of Open Access Journals (Sweden)

    Marie-Theres eSchmid

    2014-08-01

    Full Text Available During brain development, radial glial cells possess an apico-basal polarity and are coupled by adherens junctions to an F-actin belt. To elucidate the role of the actin, we conditionally deleted the key component α-E-catenin in the developing cerebral cortex. Deletion at early stages resulted in severe disruption of tissue polarity due to uncoupling of adherens junctions with the intracellular actin fibers leading to the formation of subcortical band heterotopia. Interestingly, this phenotype closely resembled the phenotype obtained by conditional RhoA deletion, both in regard to the macroscopic subcortical band heterotopia and the subcellular increase in G-actin/F-actin ratio. These data therefore together corroborate the role of the actin cytoskeleton and its anchoring to the adherens junctions for neuronal migration disorders.

  15. Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard

    2010-01-01

    As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...... two different sets of interneurons. Our data imply that for a given cortical area the amplitude of vascular signals will depend critically on the type of input and hence on the type of neurons activated. In the second study I investigated the effect of cortical spreading depression (CSD) on the evoked...... parameters as well as on neurovascular coupling. A preserved neurometabolic coupling in the wake of CSD was evident in the TC network. During CSD intracellular Ca2+ concentration increases. This amongst other factors increases the likelihood of activation of the calcineurin pathway (CaN) and opening...

  16. Influence of High Blood Pressure on Microcirculation in Cerebral Cortex of Young Rats.

    Science.gov (United States)

    Sokolova, I B; Sergeev, I V; Dvoretskii, D P

    2016-01-01

    We studied the density and structure of the microvascular network of the pia mater, the blood flow rate and oxygen saturation in the sensorimotor cortex of young spontaneously hypertensive rats (SHR). The density of the microvascular network in hypertensive animals was by ~1.4 times lower than in normotensive Wistar-Kyoto rats (control) and arteriolar bed density was lower by ~1.9 times. The blood flow rate in tissue and oxygen saturation in the sensorimotor cortex in SHR rats were significantly lower than in control animals.

  17. Targeted Inactivation of Bax Reveals a Subtype-Specific Mechanism of Cajal-Retzius Neuron Death in the Postnatal Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Fanny Ledonne

    2016-12-01

    Full Text Available Cajal-Retzius cells (CRs, the first-born neurons in the developing cerebral cortex, coordinate crucial steps in the construction of functional circuits. CRs are thought to be transient, as they disappear during early postnatal life in both mice and humans, where their abnormal persistence is associated with pathological conditions. Embryonic CRs comprise at least three molecularly and functionally distinct subtypes: septum, ventral pallium/pallial-subpallial boundary (PSB, and hem. However, whether subtype-specific features exist postnatally and through which mechanisms they disappear remain unknown. We report that CR subtypes display unique distributions and dynamics of death in the postnatal mouse cortex. Surprisingly, although all CR subtypes undergo cell death, septum, but not hem, CRs die in a Bax-dependent manner. Bax-inactivated rescued septum-CRs maintain immature electrophysiological properties. These results underlie the existence of an exquisitely refined control of developmental cell death and provide a model to test the effect of maintaining immature circuits in the adult neocortex.

  18. A muscle-derived factor(s) induces expression of a catecholamine phenotype in neurons of cultured rat cerebral cortex.

    Science.gov (United States)

    Iacovitti, L; Evinger, M J; Joh, T H; Reis, D J

    1989-10-01

    We sought to determine the source of the signal(s) that promotes expression of the catecholamine (CA) enzyme tyrosine hydroxylase (TH) in cultured neurons of embryonic rat cerebral cortex, a tissue which is not thought to contain CA cells in vivo. Cortical neurons were cultured with their non-neuronal constituents and 48 hr later immunostained for TH. Fibroblasts or glia had no effects, however, blood vessels increased the numbers of TH neurons nearly 4-fold. Coculture with either perinatal aorta, skeletal or cardiac muscle, clonal muscle cell lines 1440 (smooth) and L6 (skeletal), conditioned media from L6 cells, or a soluble extract of L6 cells increased the number of TH neurons up to 20-fold. The induction of TH by muscle extract was (1) dose dependent; (2) paralleled by a proportional increase in the steady-state levels of TH mRNA; (3) greatly reduced by the RNA synthesis inhibitor alpha-amanitin or the protein synthesis inhibitor cycloheximide; and (4) unassociated with change in the survival of neurons in culture. The response was not replicated by treatment with other established neurotrophic substances, including NGF, EGF, FGF, PDGF, neuroleukin, insulin, pyruvate, KCI, adenosine, or inosine. We conclude that muscle contains a potentially novel substance, muscle-derived differentiation factor (MDF) that promotes differentiation but not survival of neurons of cerebral cortex by de novo synthesis of TH mRNA and TH protein. Thus, neurons of the CNS, as in periphery, may undergo phenotypic interconversion in response to biologically derived molecules in their environment.

  19. Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex.

    Science.gov (United States)

    Bellesi, Michele; de Vivo, Luisa; Chini, Mattia; Gilli, Francesca; Tononi, Giulio; Cirelli, Chiara

    2017-05-24

    We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements of synapses and surrounding astrocytic processes in mouse frontal cortex after 6-8 h of sleep, spontaneous wake, or sleep deprivation (SD) and after chronic (∼5 d) sleep restriction (CSR). Astrocytic phagocytosis, mainly of presynaptic components of large synapses, increased after both acute and chronic sleep loss relative to sleep and wake. MERTK expression and lipid peroxidation in synaptoneurosomes also increased to a similar extent after short and long sleep loss, suggesting that astrocytic phagocytosis may represent the brain's response to the increase in synaptic activity associated with prolonged wake, clearing worn components of heavily used synapses. Using confocal microscopy, we then found that CSR but not SD mice show morphological signs of microglial activation and enhanced microglial phagocytosis of synaptic elements, without obvious signs of neuroinflammation in the CSF. Because low-level sustained microglia activation can lead to abnormal responses to a secondary insult, these results suggest that chronic sleep loss, through microglia priming, may predispose the brain to further damage.SIGNIFICANCE STATEMENT We find that astrocytic phagocytosis of synaptic elements, mostly of presynaptic origin and in large synapses, is upregulated already after a few hours of sleep deprivation and shows a further significant increase after prolonged and

  20. [Stereological investigation in the cerebral cortex of aging subjects (author's transl)].

    Science.gov (United States)

    Hunziker, O; Abdel'Al, S; Schulz, U; Meier-Ruge, W

    1978-09-01

    Involving cortical regions, capillaries of the human cerebrum of two 19 and 27 years old men, a 69 years old woman and a 72 years old man were stereologically investigated by optical-electronic image-analysis. The cortical capillary net work was demonstrated by the alkaline phosphatase activity. Each cortex region comprised a determination of the stereological parameters diameter, projected area, specific surface area, capillary distances in linear direction of TV-lines and total length per unit cortex volume. A comparison between different cortex regions revealed a good correlation between increased values of the diameter and the projected area, a decreased specific surface area and diminished capillary distances, which entail a shortened distance of oxygen diffusion through the cortical tissue. During aging a diminished capillary surface area, which results from increased values of diameter and projected area is compensated by shortened capillary distances. Presumably an augmented capillary length is due to a condensation of the capillary net per unit cortex tissue. The behaviour of the registered stereological parameters seems to be an accommodation of the capillary net in the human cerebrum to metabolic and circulatory changes during aging.

  1. Cortical chemoarchitecture shapes macroscale effective functional connectivity patterns in macaque cerebral cortex

    NARCIS (Netherlands)

    Turk, Elise; Scholtens, Lianne H.; van den Heuvel, Martijn P.

    The mammalian cortex is a complex system of-at the microscale level-interconnected neurons and-at the macroscale level-interconnected areas, forming the infrastructure for local and global neural processing and information integration. While the effects of regional chemoarchitecture on local

  2. Neurofilament and glial alterations in the cerebral cortex in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Troost, D.; Sillevis Smitt, P. A.; de Jong, J. M.; Swaab, D. F.

    1992-01-01

    According to the literature, only minor nonspecific histopathological lesions are present in the motor cortex in up to 90% of the amyotrophic lateral sclerosis (ALS) patients. These observations, however, have so far been based mainly on conventional staining techniques. An exception to this is the

  3. Middle cerebral artery stenosis associated with moyamoya pattern collateralization

    Directory of Open Access Journals (Sweden)

    Randall Edgell

    2010-11-01

    Full Text Available Background and Purpose: Moyamoya disease is a well described phenomenon presenting with terminal internal carotid artery occlusion and rete pattern of collateralization around the occlusion. The development of moyamoya-like collaterals secondary to isolated middle cerebral artery stenosis or occlusion and the natural history of this entity in Caucasians have not been well described. Methods: Cerebral angiograms and CT angiograms performed between August 2004 and August of 2006 demonstrating moyamoya collateralization at a single US center were retrospectively reviewed. All cases of middle cerebral artery stenosis associated with a rete pattern of collateralization were included in this series. Demographic, clinical, and angiographic data were obtained. Results: There were 3 cases of middle cerebral artery stenosis associated with a moyamoya pattern of collateralization. The average age of the patients was 36 years old, 2 were male, and all were Caucasian. All patients presented with ischemic symptoms. The average degree of stenosis was 91%. No stenosis was seen in the supraclinoid internal carotid arteries or elsewhere in the intracranial vasculature. Conclusion: We describe a moyamoya-like pattern of anastomosis associated with isolated severe middle cerebral artery stenosis or occlusion in Caucasians.

  4. Difference of language cortex reorganization between cerebral arteriovenous malformations, cavernous malformations, and gliomas: a functional MRI study.

    Science.gov (United States)

    Deng, Xiaofeng; Xu, Long; Zhang, Yan; Wang, Bo; Wang, Shuo; Zhao, Yuanli; Cao, Yong; Zhang, Dong; Wang, Rong; Ye, Xun; Wu, Jun; Zhao, Jizong

    2016-04-01

    The authors attempted to demonstrate the difference in language cortex reorganization between cerebral malformations (AVMs), cavernous malformations (CMs), and gliomas by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Clinical and imaging data of 27 AVM patients (AVM-L group), 29 CM patients (CM-L group), and 20 glioma patients (Glioma-L group) were retrospectively reviewed, with lesions overlying the left inferior frontal gyrus (Broca area). As a control, patients with lesions involving the right inferior frontal gyrus were also enrolled, including 14 AVM patients (AVM-R group), 20 CM patients (CM-R group), and 14 glioma patients (Glioma-R group). All patients were right-handed. Lateralization indices (LI) of BOLD signal activations were calculated separately for Broca and Wernicke areas. In AVM-L group, right-sided lateralization of BOLD signals was observed in 10 patients (37.0%), including 6 in the Broca area alone, 1 in the Wernicke area alone, and 3 in both areas. Three patients (10.3%) of CM-L group showed right-sided lateralization in both Broca and Wernicke areas, and 1 patient (5.0%) of Glioma-L group had right-sided lateralization in the Wernicke area alone. A significant difference of right-sided lateralization was observed between the AVM-L group and CM-L group (P = 0.018) and also between the AVM-L group and Glioma-L group (P = 0.027). No patient in AVM-R, CM-R, or Glioma-R groups showed right-sided lateralization. Language cortex reorganization may occur in AVM, CM, and glioma patients when the traditional language cortex was involved by lesions, but the potential of reorganization for CM and glioma patients seems to be insufficient compared with AVM patients.

  5. Visual predictions in the orbitofrontal cortex rely on associative content.

    Science.gov (United States)

    Chaumon, Maximilien; Kveraga, Kestutis; Barrett, Lisa Feldman; Bar, Moshe

    2014-11-01

    Predicting upcoming events from incomplete information is an essential brain function. The orbitofrontal cortex (OFC) plays a critical role in this process by facilitating recognition of sensory inputs via predictive feedback to sensory cortices. In the visual domain, the OFC is engaged by low spatial frequency (LSF) and magnocellular-biased inputs, but beyond this, we know little about the information content required to activate it. Is the OFC automatically engaged to analyze any LSF information for meaning? Or is it engaged only when LSF information matches preexisting memory associations? We tested these hypotheses and show that only LSF information that could be linked to memory associations engages the OFC. Specifically, LSF stimuli activated the OFC in 2 distinct medial and lateral regions only if they resembled known visual objects. More identifiable objects increased activity in the medial OFC, known for its function in affective responses. Furthermore, these objects also increased the connectivity of the lateral OFC with the ventral visual cortex, a crucial region for object identification. At the interface between sensory, memory, and affective processing, the OFC thus appears to be attuned to the associative content of visual information and to play a central role in visuo-affective prediction. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Cerebral aneurysm associated with cardiac myxoma: Case Report

    Science.gov (United States)

    Ivanović, Branislava A.; Tadić, Marijana; Vraneš, Mile; Orbović, Bojana

    2011-01-01

    Left atrial myxomas are a rare but well known cause of cerebrovascular accidents in young people. Cerebral embolism is the most common cause of cerebral ischemic stroke. The intracranial aneurysm is rarely associated with myxoma. We report the case of a patient who had an operation of PICA aneurysm due to subarachnoid hemorrhage ten months before the discovery of the large left atrial myxoma. Fortunately, the untimely diagnosis of the myxoma did not have other consequences. In order to prevent possible complications of we should keep in mind that these two apparently different entities could be associated. PMID:21342146

  7. Cerebral aneurysm associated with cardiac myxoma: Case Report

    Directory of Open Access Journals (Sweden)

    Branislava A. Ivanović

    2011-02-01

    Full Text Available Left atrial myxomas are a rare but well known cause of cerebrovascular accidents in young people. Cerebral embolism is the most common cause of cerebral ischemic stroke. The intracranial aneurysm is rarely associated with myxoma. We report the case of a patient who had an operation of PICA aneurysm due to subarachnoid hemorrhage ten months before the discovery of the large left atrial myxoma. Fortunately, the untimely diagnosis of the myxoma did not have other consequences. In order to prevent possible complications of we should keep in mind that these two apparently different entities could be associated.

  8. Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fox, P.T.; Raichle, M.E.

    1984-05-01

    The purpose of this investigation was to determine the relationship between the repetition rate of a simple sensory stimulus and regional cerebral blood flow (rCBF) in the human brain. Positron emission tomography (PET), using intravenously administered H/sub 2/(/sup 15/)O as the diffusible blood-flow tracer, was employed for all CBF measurements. The use of H/sub 2/(/sup 15/)O with PET allowed eight CBF measurements to be made in rapid sequence under multiple stimulation conditions without removing the subject from the tomograph. Nine normal volunteers each underwent a series of eight H2(/sup 15/)O PET measurements of CBF. Initial and final scans were made during visual deprivation. The six intervening scans were made during visual activation with patterned-flash stimuli given in random order at 1.0-, 3.9-, 7.8-, 15.5-, 33.1-, and 61-Hz repetition rates. The region of greatest rCBF increase was determined. Within this region the rCBF was determined for every test condition and then expressed as the percentage change from the value of the initial unstimulated scan (rCBF% delta). In every subject, striate cortex rCBF% delta varied systematically with stimulus rate. Between 0 and 7.8 Hz, rCBF% delta was a linear function of stimulus repetition rate. The rCBF response peaked at 7.8 Hz and then declined. The rCBF% delta during visual stimulation was significantly greater than that during visual deprivation for every stimulus rate except 1.0 Hz. The anatomical localization of the region of peak rCBF response was determined for every subject to be the mesial occipital lobes along the calcarine fissure, primary visual cortex. Stimulus rate is a significant determinant of rCBF response in the visual cortex. Investigators of brain responses to selective activation procedures should be aware of the potential effects of stimulus rate on rCBF and other measurements of cerebral metabolism.

  9. Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution

    Directory of Open Access Journals (Sweden)

    M.G.P. Rosa

    2002-12-01

    Full Text Available In this paper, the topology of cortical visuotopic maps in adult primates is reviewed, with emphasis on recent studies. The observed visuotopic organisation can be summarised with reference to two basic rules. First, adjacent radial columns in the cortex represent partially overlapping regions of the visual field, irrespective of whether these columns are part of the same or different cortical areas. This primary rule is seldom, if ever, violated. Second, adjacent regions of the visual field tend to be represented in adjacent radial columns of a same area. This rule is not as rigid as the first, as many cortical areas form discontinuous, second-order representations of the visual field. A developmental model based on these physiological observations, and on comparative studies of cortical organisation, is then proposed, in order to explain how a combination of molecular specification steps and activity-driven processes can generate the variety of visuotopic organisations observed in adult cortex.

  10. Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

    Directory of Open Access Journals (Sweden)

    Seiki Tajima

    2010-01-01

    Full Text Available Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H2O  15 positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11. Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.

  11. Age-dependent changes in distribution of P3a/P3b amplitude and thickness of the cerebral cortex.

    Science.gov (United States)

    Fjell, Anders M; Walhovd, Kristine B; Reinvang, Ivar

    2005-09-08

    With increasing age, the electrophysiological event-related potentials P3a/P3b tend to get a more frontal maximum. The cognitive significance of this so-called frontal shift is not known, but hypotheses have focused on changes in the integrity of the frontal lobes. The aim of the present study was to test how the thickness of the cerebral cortex is related to the frontal shift. Well screened elderly participants went through a visual three-stimuli oddball-task, a battery of neuropsychological tests and magnetic resonance imaging scans. It was found that participants with frontocentral maxima had a thicker cerebral cortex in distinct areas than participants with parietal maxima, both for P3a and for P3b, while the parietal P3b participants had a thicker cortex in the anterior cingulate. This is the first study to demonstrate that age-dependent changes in the scalp distribution of electrophysiological activity are related to differences in thickness of the cerebral cortex.

  12. Induction of oxidative stress and inhibition of superoxide dismutase expression in rat cerebral cortex and cerebellum by PTU-induced hypothyroidism and its reversal by curcumin.

    Science.gov (United States)

    Jena, Srikanta; Anand, Chinmay; Chainy, Gagan Bihari Nityananda; Dandapat, Jagneshwar

    2012-08-01

    The present study was carried out to elucidate the effectiveness of curcumin in ameliorating the expression of superoxide dismutase (SOD) in cerebral cortex and cerebellum of rat brain under 6-propyl-2-thiouracil (PTU)-induced hypothyroidism. Induction of hypothyroidism in adult rats by PTU resulted in augmentation of lipid peroxidation (LPx), an index of oxidative stress in cerebellum but not in cerebral cortex. Curcumin-supplementation to PTU-treated (hypothyroid) rats showed significant reduction in the level of LPx in both the regions of brain. The decreased translated products (SOD1 and SOD2) and the unchanged activity of SOD in cerebral cortex of PTU-treated rats were increased on supplementation of curcumin to the hypothyroid rats. Declined translated products of SOD1 and SOD2 in cerebellum of PTU-treated rats were alleviated on administration of curcumin to hypothyroid rats. On the other hand, the decreased activity of SOD in cerebellum of PTU-treated rats was further declined on administration of curcumin to the hypothyroid rats. Results of the present investigation indicate that curcumin differentially modulates the expression of superoxide dismutase in rat brain cortex and cerebellum under PTU-induced hypothyroidism.

  13. Migraine with visual aura associated with thicker visual cortex.

    Science.gov (United States)

    Gaist, David; Hougaard, Anders; Garde, Ellen; Reislev, Nina Linde; Wiwie, Rikke; Iversen, Pernille; Madsen, Camilla Gøbel; Blaabjerg, Morten; Nielsen, Helle Hvilsted; Krøigård, Thomas; Østergaard, Kamilla; Kyvik, Kirsten Ohm; Hjelmborg, Jacob; Madsen, Kristoffer; Siebner, Hartwig Roman; Ashina, Messoud

    2018-01-18

    Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura, suggesting that such structural alterations were either due to increased neuronal density in the areas involved, or a result of multiple episodes of cortical spreading depression as part of aura attacks. Subsequent studies have yielded conflicting results, possibly due to methodological reasons, e.g. small number of subjects. In this cross-sectional study, we recruited females aged 30-60 years from the nationwide Danish Twin Registry. Brain MRI of females with migraine with aura (patients), their co-twins, and unrelated migraine-free twins (controls) were performed at a single centre and assessed for cortical thickness in predefined cortical areas (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The difference in cortical thickness between patients and controls adjusted for age, and other potential confounders was assessed. Comparisons of twin pairs discordant for migraine with aura were also performed. Comparisons were based on 166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence interval 0.008 to 0.067)], while differences in the remaining areas examined were not statistically significant [adjusted mean difference (95% confidence interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0

  14. Association of Maternal Obesity with Child Cerebral Palsy or Death.

    Science.gov (United States)

    McPherson, Jessica A; Smid, Marcela C; Smiley, Sarah; Stamilio, David M

    2017-05-01

    Objective  The primary aim of this study was to determine if there is an association between maternal obesity and cerebral palsy or death in children. Study Design  This is a retrospective cohort analysis of a randomized controlled clinical trial previously performed by the Maternal-Fetal Medicine Units Network. Women in the original trial were included if at high risk for preterm delivery. The present study included singletons enrolled in the original study with complete data. Obese and nonobese women were compared. A secondary analysis comparing class 3 obese or classes 1 to 2 obese women to nonobese women was performed. The primary outcome was a composite of cerebral palsy or perinatal death. Results  In this study, 1,261 nonobese, 339 obese, and 69 morbidly obese women were included. When adjusted for gestational age at delivery and magnesium exposure, there was no association between maternal obesity and child cerebral palsy or death. In the analysis using obesity severity categories, excess risk for adverse outcome appeared confined to the class 3 obese group. Conclusion  In women at high risk of delivering preterm, maternal obesity was not independently associated with child cerebral palsy or death. The association in unadjusted analysis appears to be mediated by preterm birth among obese patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Some economic and socio-cultural factors associated with cerebral ...

    African Journals Online (AJOL)

    Introduction: Risk factors associated with the occurrence of cerebral malaria in under fives are well documented. Outside these acknowledged factors of age, location, and nutrition, other socioeconomic/cultural factors could contribute to the maze of factors determining the occurrence of the morbidity. Methods: To unravel ...

  16. Visual space and object space in the cerebral cortex of retinal disease patients.

    Directory of Open Access Journals (Sweden)

    Elfi Goesaert

    Full Text Available The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings. This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration, and a patient where input to the peripheral retina is lost (retinitis pigmentosa. From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline rather than relative activation (comparing different stimulus conditions. Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (deactivation is consistent with the retinal loss.

  17. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  18. Cell Type-specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex

    Science.gov (United States)

    Zhang, Xiaochang; Chen, Ming Hui; Wu, Xuebing; Kodani, Andrew; Fan, Jean; Doan, Ryan; Ozawa, Manabu; Ma, Jacqueline; Yoshida, Nobuaki; Reiter, Jeremy F.; Black, Douglas L.; Kharchenko, Peter V.; Sharp, Phillip A.; Walsh, Christopher A.

    2017-01-01

    SUMMARY Alternative splicing is prevalent in the mammalian brain. To interrogate the functional role of alternative splicing in neural development, we analyzed purified neural progenitor cells (NPCs) and neurons from developing cerebral cortices, revealing hundreds of differentially spliced exons that preferentially alter key protein domains—especially in cytoskeletal proteins—and can harbor disease-causing mutations. We show that Ptbp1 and Rbfox proteins antagonistically govern the NPC-to-neuron transition by regulating neuron-specific exons. While Ptbp1 maintains apical progenitors partly through suppressing a poison exon of Flna in NPCs, Rbfox proteins promote neuronal differentiation by switching Ninein from a centrosomal splice form in NPCs to a non-centrosomal isoform in neurons. We further uncover an intronic human mutation within a PTBP1 binding site that disrupts normal skipping of the FLNA poison exon in NPCs and causes a brain-specific malformation. Our study indicates that dynamic control of alternative splicing governs cell fate in cerebral cortical development. PMID:27565344

  19. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex.

    Science.gov (United States)

    Zhang, Xiaochang; Chen, Ming Hui; Wu, Xuebing; Kodani, Andrew; Fan, Jean; Doan, Ryan; Ozawa, Manabu; Ma, Jacqueline; Yoshida, Nobuaki; Reiter, Jeremy F; Black, Douglas L; Kharchenko, Peter V; Sharp, Phillip A; Walsh, Christopher A

    2016-08-25

    Alternative splicing is prevalent in the mammalian brain. To interrogate the functional role of alternative splicing in neural development, we analyzed purified neural progenitor cells (NPCs) and neurons from developing cerebral cortices, revealing hundreds of differentially spliced exons that preferentially alter key protein domains-especially in cytoskeletal proteins-and can harbor disease-causing mutations. We show that Ptbp1 and Rbfox proteins antagonistically govern the NPC-to-neuron transition by regulating neuron-specific exons. Whereas Ptbp1 maintains apical progenitors partly through suppressing a poison exon of Flna in NPCs, Rbfox proteins promote neuronal differentiation by switching Ninein from a centrosomal splice form in NPCs to a non-centrosomal isoform in neurons. We further uncover an intronic human mutation within a PTBP1-binding site that disrupts normal skipping of the FLNA poison exon in NPCs and causes a brain-specific malformation. Our study indicates that dynamic control of alternative splicing governs cell fate in cerebral cortical development. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Regional and laminar distribution of the dopamine and serotonin innervation in the macaque cerebral cortex: a radioautographic study

    Energy Technology Data Exchange (ETDEWEB)

    Berger, B.; Trottier, S.; Verney, C.; Gaspar, P.; Alvarez, C.

    1988-07-01

    The regional density and laminar distribution of dopamine (DA) and serotonin (5-HT) afferents were investigated in the cerebral cortex of cynomolgus monkeys using a radioautographic technique that is based on the high affinity uptake capacity of these aminergic neurons. Large vibratome sections, 50 micron thick, were incubated with (3H) DA (0.2 microM) and desipramine (5 microM) or with unlabeled norepinephrine (5 microM) and (3H) 5-HT (0.6 microM), which allowed for the specific labeling of the DA and 5-HT innervations, respectively. After fixation, these sections were dried, defatted, and radioautographed by dipping. Semiquantitative data on the DA innervation also were provided by counting (3H) DA-labeled axonal varicosities in radioautographs from 4-micron-thick sections of the slices obtained after epon embedding. The DA innervation was widespread and differed in density and laminar distribution in the agranular and granular cortices. DA afferents were densest in the anterior cingulate (area 24) and the motor areas (areas 4, 6, and supplementary motor area (SMA)). In the latter they displayed a trilaminar pattern of distribution, predominating in layers I, IIIa, and V-VI, with characteristic cluster-like formations in layer IIIa, especially in the medial part of motor areas. In the granular prefrontal (areas 46, 9, 10, 11, 12), parietal (areas 1, 2, 3, 5, 7), temporal (areas 21, 22), and posterior cingulate (area 23) cortices, DA afferents were less dense and showed a bilaminar pattern of distribution, predominating in the depth of layer I and in layers V-VI; density in layers II, III, and IV was only 20% of that in layer I. The lowest density was in the visual cortex, particularly in area 17, where the DA afferents were almost restricted to layer I.

  1. Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Drew, Paul D; Johnson, Jennifer W; Douglas, James C; Phelan, Kevin D; Kane, Cynthia J M

    2015-03-01

    Fetal alcohol spectrum disorders (FASD) result from fetal exposure to alcohol and are the leading cause of mental retardation in the United States. There is currently no effective treatment that targets the causes of these disorders. Thus, novel therapies are critically needed to limit the neurodevelopmental and neurodegenerative pathologies associated with FASD. A neonatal mouse FASD model was used to examine the role of the neuroimmune system in ethanol (EtOH)-induced neuropathology. Neonatal C57BL/6 mice were treated with EtOH, with or without pioglitazone, on postnatal days 4 through 9, and tissue was harvested 1 day post treatment. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits anti-inflammatory activity and is neuroprotective. We compared the effects of EtOH with or without pioglitazone on cytokine and chemokine expression and microglial morphology in the hippocampus, cerebellum, and cerebral cortex. In EtOH-treated animals compared with controls, cytokines interleukin-1β and tumor necrosis factor-α mRNA levels were increased significantly in the hippocampus, cerebellum, and cerebral cortex. Chemokine CCL2 mRNA was increased significantly in the hippocampus and cerebellum. Pioglitazone effectively blocked the EtOH-induced increase in the cytokines and chemokine in all tissues to the level expressed in handled-only and vehicle-treated control animals. EtOH also produced a change in microglial morphology in all brain regions that was indicative of microglial activation, and pioglitazone blocked this EtOH-induced morphological change. These studies indicate that EtOH activates microglia to a pro-inflammatory stage and also increases the expression of neuroinflammatory cytokines and chemokines in diverse regions of the developing brain. Further, the anti-inflammatory and neuroprotective PPAR-γ agonist pioglitazone blocked these effects. It is proposed that microglial activation and inflammatory molecules expressed

  2. Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex.

    Science.gov (United States)

    Villa, R F; Gorini, A; Hoyer, S

    2006-11-01

    The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

  3. Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates

    Science.gov (United States)

    Ribeiro, Pedro F. M.; Manger, Paul R.; Catania, Kenneth C.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2014-01-01

    The olfactory bulb is an evolutionarily old structure that antedates the appearance of a six-layered mammalian cerebral cortex. As such, the neuronal scaling rules that apply to scaling the mass of the olfactory bulb as a function of its number of neurons might be shared across mammalian groups, as we have found to be the case for the ensemble of non-cortical, non-cerebellar brain structures. Alternatively, the neuronal scaling rules that apply to the olfactory bulb might be distinct in those mammals that rely heavily on olfaction. The group previously referred to as Insectivora includes small mammals, some of which are now placed in Afrotheria, a base group in mammalian radiation, and others in Eulipotyphla, a group derived later, at the base of Laurasiatheria. Here we show that the neuronal scaling rules that apply to building the olfactory bulb differ across eulipotyphlans and other mammals such that eulipotyphlans have more neurons concentrated in an olfactory bulb of similar size than afrotherians, glires and primates. Most strikingly, while the cerebral cortex gains neurons at a faster pace than the olfactory bulb in glires, and afrotherians follow this trend, it is the olfactory bulb that gains neurons at a faster pace than the cerebral cortex in eulipotyphlans, which contradicts the common view that the cerebral cortex is the fastest expanding structure in brain evolution. Our findings emphasize the importance of not using brain structure size as a proxy for numbers of neurons across mammalian orders, and are consistent with the notion that different selective pressures have acted upon the olfactory system of eulipotyphlans, glires and primates, with eulipotyphlans relying more on olfaction for their behavior than glires and primates. Surprisingly, however, the neuronal scaling rules for primates predict that the human olfactory bulb has as many neurons as the larger eulipotyphlan olfactory bulbs, which questions the classification of humans as microsmatic

  4. Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2017-04-01

    Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  5. Decreased IDE and IGF2 expression but increased Aβ40 in the cerebral cortex of mouse pups by early life lead exposure.

    Science.gov (United States)

    Li, Ning; Yang, Guojun; Wang, Yueying; Qiao, Mingwu; Zhang, Pingan; Shao, Jianfeng; Yang, Guoyu

    2016-03-01

    As the abbreviation of plumbum and a chemical symbol for lead, Pb produces neurotoxic effects, which result into an impairment of learning and memory and other neurological dysfunctions. However, the mechanism of neurotoxicity of Pb exposure is unclear. The present study was undertaken to investigate the effects of maternal lead exposure on expression of insulin-degrading enzyme (IDE),insulin-like growth factor 2 (IGF2) and beta amyloid protein 40 (Aβ40) in the cerebral cortex of mice offspring. Lead exposure initiated from beginning of gestation to weaning. Lead acetate administered in drinking solutions was dissolved in distilled deionized water at the concentrations of 0.1%, 0.2% and 0.5% groups respectively. On the 21st postnatal day, On the PND21, the learning and memory ability were tested by water maze test and the Pb levels were also determined by graphite furnace atomic absorption spectrometry. The expression of IDE, IGF2 and Aβ40 in cerebral cortex was examined by immunohistochemistry, immunofluorescence and western blotting. The lead levels in blood and cerebral cortex of all lead exposure groups were significantly higher than that of the control group (Plead exposure groups were worse than that of the control group (Plead exposed groups than that of the control group (Pexposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions

    Energy Technology Data Exchange (ETDEWEB)

    Conn, P.J.; Sanders-Bush, E.

    1985-07-01

    In rat cerebral cortex, serotonin (5-HT) stimulates phosphoinositide turnover with an EC50 of 1 microM in the presence of pargyline. The EC50 is 16-fold higher in the absence of pargyline. Selective S2 antagonists inhibit 5-HT-stimulated phosphoinositide turnover. Schild analysis of the blockade by ketanserin of the 5-HT effect gives an estimated Kd of ketanserin for the phosphoinositide-linked receptor of 11.7 nM, which agrees with the Kd (3.5 nM) of (/sup 3/H)ketanserin for the S2 site. Furthermore, MK-212, 5-HT and 5-fluorotryptamine stimulate phosphoinositide turnover with potencies that resemble their potencies at the S2 but not the S1 binding site. Of 11 agonists tested, the tryptamine derivatives tend to be more efficacious than the piperazine derivatives. The selective S1 agonist 8-hydroxy-2-(di-N-propylamino)tetralin is inactive at stimulating phosphoinositide turnover. No significant relationship exists between the regional distributions of 5-HT-stimulated phosphoinositide turnover and S2 binding sites. Furthermore, the S2 antagonist ketanserin is less potent and less efficacious in hippocampus and limbic forebrain than in cerebral cortex. These data suggest that 5-HT-stimulated phosphoinositide turnover is linked to the S2 binding site in rat cerebral cortex. However, 5-HT increases phosphoinositide turnover in subcortical regions by mechanisms other than stimulation of the S2 receptor.

  7. [Comparative experimental study of the influence of drugs that improve brain metabolism (angiogen, cytoflavin) on neuronal apoptosis and function of cerebral cortex during aging].

    Science.gov (United States)

    Bazhanova, E D; Anisimov, V N; Sukhanov, D S; Teplyĭ, D L

    2015-01-01

    The safety of cortical neurons and their functional activity is essential for organism at all stages of ontogenesis. However, aging changes leading to an increase in apoptosis level may cause considerable damage to cerebral cortex function, including sensorimotor. We have studied the role of exogenous neurometabolites (angiogen, cytoflavin) in apoptosis regulation and correction of age-related motor and behavioral disturbances. To study the regulation of neuronal morphofunctional activity, we used accelerate-senescent transgenic HER2 mice in comparison to wild type FBV mice. Functional changes in cerebral cortex were studied by the Suok test and open field test, the level of neuronal apoptosis was assessed by TUNEL method, the expression of apoptosis-modulating proteins was detected by immunohistochemistry and Western blotting. We have revealed differences in psycho-emotional and locomotor activity of these strains of mice. In addition, results of our study showed morphological differences: increase in the apoptosis level of cortical neurons in aged FBV type mice, but no changes in aged HER2 mice. The investigated drugs induce cell death of cortical neurons in transgenic mice of both ages and in young wild-type mice by p53-dependent pathway. Increased apoptosis in the cortex of old transgenic mice has important clinical implications, because reduced apoptosis during aging is one of the causes of cancer. The treatment of old wild-type animals reduces elevated neuronal apoptosis, which decreases risk of age neurodegeneration. Thus, revealed morphological changes in the cerebral cortex are the basis for involutional disabilities (including reduced locomotor activity and increased anxiety level). The use of angiogen and cytoflavin treatment improves functional activity of the cortex and protects normal structure of nervous tissue.

  8. Down-regulation of sup 3 H-imipramine binding sites in rat cerebral cortex prenatal exposure to antidepressants

    Energy Technology Data Exchange (ETDEWEB)

    Montero, D.; de Ceballos, M.L. (Cajal Institute, Madrid (Spain)); Del Rio, J. (Univ. of Navarra, Pamplona (Spain))

    1990-01-01

    Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and {sup 3}H-imipramine binding ({sup 3}H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of {sup 3}H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. After chronic treatment of adult animals, only chlorimipramine was able to down-regulate the {sup 3}H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical {sup 3}H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants.

  9. Joint Spectral Decomposition for the Parcellation of the Human Cerebral Cortex Using Resting-State fMRI.

    Science.gov (United States)

    Arslan, Salim; Parisot, Sarah; Rueckert, Daniel

    2015-01-01

    Identification of functional connections within the human brain has gained a lot of attention due to its potential to reveal neural mechanisms. In a whole-brain connectivity analysis, a critical stage is the computation of a set of network nodes that can effectively represent cortical regions. To address this problem, we present a robust cerebral cortex parcellation method based on spectral graph theory and resting-state fMRI correlations that generates reliable parcellations at the single-subject level and across multiple subjects. Our method models the cortical surface in each hemisphere as a mesh graph represented in the spectral domain with its eigenvectors. We connect cortices of different subjects with each other based on the similarity of their connectivity profiles and construct a multi-layer graph, which effectively captures the fundamental properties of the whole group as well as preserves individual subject characteristics. Spectral decomposition of this joint graph is used to cluster each cortical vertex into a subregion in order to obtain whole-brain parcellations. Using rs-fMRI data collected from 40 healthy subjects, we show that our proposed algorithm computes highly reproducible parcellations across different groups of subjects and at varying levels of detail with an average Dice score of 0.78, achieving up to 9% better reproducibility compared to existing approaches. We also report that our group-wise parcellations are functionally more consistent, thus, can be reliably used to represent the population in network analyses.

  10. Gallium nitride induces neuronal differentiation markers in neural stem/precursor cells derived from rat cerebral cortex.

    Science.gov (United States)

    Chen, Chi-Ruei; Li, Yi-Chen; Young, Tai-Horng

    2009-09-01

    In the present study, gallium nitride (GaN) was used as a substrate to culture neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral cortex, to examine the effect of GaN on the behavior of NSPCs in the presence of basic fibroblast growth factor (bFGF) in serum-free medium. Morphological studies showed that neurospheres maintained their initial shape and formed many long and thick processes with the fasciculate feature on GaN. Immunocytochemical characterization showed that GaN could induce the differentiation of NSPCs into neurons and astrocytes. Compared to poly-d-lysine (PDL), the most common substrate used for culturing neurons, there was considerable expression of synapsin I for differentiated neurons on GaN, suggesting GaN could induce the differentiation of NSPCs towards the mature differentiated neurons. Western blot analysis showed that the suppression of glycogen synthase kinase-3beta (GSK-3beta) activity was one of the effects of GaN-promoted NSPC differentiation into neurons. Finally, compared to PDL, GaN could significantly improve cell survival to reduce cell death after long-term culture. These results suggest that GaN potentially has a combination of electric characteristics suitable for developing neuron and/or NSPC chip systems.

  11. Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.

    Science.gov (United States)

    Sogut, Ibrahim; Uysal, Onur; Oglakci, Aysegul; Yucel, Ferruh; Kartkaya, Kazim; Kanbak, Gungor

    2017-03-01

    Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

  12. JIP3 regulates neuronal radial migration by mediating TrkB axonal anterograde transport in the developing cerebral cortex.

    Science.gov (United States)

    Ma, Huixian; Yu, Hui; Li, Ting; Zhao, Yan; Hou, Ming; Chen, Zheyu; Wang, Yue; Sun, Tao

    2017-04-15

    Radial migration is essential for the precise lamination and the coordinated function of the cerebral cortex. However, the molecular mechanisms for neuronal radial migration are not clear. Here, we report that c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) is highly expressed in the brain of embryonic mice and essential for radial migration. Knocking down JIP3 by in utero electroporation specifically perturbs the radial migration of cortical neurons but has no effect on neurogenesis and neuronal differentiation. Furthermore, we illustrate that JIP3 knockdown delays but does not block the migration of cortical neurons by investigating the distribution of neurons with JIP3 knocked down in the embryo and postnatal mouse. Finally, we find that JIP3 regulates cortical neuronal migration by mediating TrkB axonal anterograde transport during brain development. These findings deepen our understanding of the regulation of neuronal development by JIP3 and provide us a novel view on the regulating mechanisms of neuronal radial migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The association between inherited cytokine polymorphisms and cerebral palsy.

    Science.gov (United States)

    Gibson, Catherine S; MacLennan, Alastair H; Goldwater, Paul N; Haan, Eric A; Priest, Kevin; Dekker, Gustaaf A

    2006-03-01

    The purpose of this study was to investigate associations between inherited cytokine polymorphisms and cerebral palsy. This was a case-control study that used DNA from the newborn infant screening cards of 443 white infants with cerebral palsy and 883 white control infants to test for the following cytokine polymorphisms: tumor necrosis factor-alpha-308, mannose-binding lectin-221, and 3 polymorphisms in exon-1 of the mannose-binding lectin gene at codon-52, -54, and -57. At all gestational ages mannose-binding lectin codon-54 increased the risk of the development of diplegia (homozygous or heterozygous odds ratio, 1.55; 95% CI, 1.03-2.32). For babies who were born at term, the risk of the development of quadriplegia was associated with heterozygous tumor necrosis factor-alpha (odds ratio, 1.82; 95% CI, 1.04-3.15), and mannose-binding lectin codon-54 was associated with diplegia (homozygous or heterozygous odds ratio, 2.12; 95% CI, 1.10-4.05). The presence of any polymorphism in mannose-binding lectin exon-1 at term approximately doubled the risk of the development of diplegia (odds ratio, 1.94; 95% CI, 1.05-3.62). Homozygous or heterozygous tumor necrosis factor-alpha was associated with hemiplegia for babies who were born at <32 weeks of gestation (odds ratio, 2.38; 95% CI, 1.02-5.58). Overall, the presence of any cytokine polymorphism was associated with cerebral palsy (odds ratio, 1.37; 95% CI, 1.02-1.84). Carriage of polymorphisms in the tumor necrosis factor-alpha and mannose-binding lectin genes are associated with an increased risk of cerebral palsy.

  14. Therapeutic effects of functional electrical stimulation on motor cortex in children with spastic Cerebral Palsy.

    Science.gov (United States)

    Mukhopadhyay, R; Mahadevappa, M; Lenka, P K; Biswas, A

    2015-01-01

    In the present study we have evaluated the electroencephalogram (EEG) signal recorded during ankle dorsal and plantar flexion in children with spastic Cerebral Palsy (CP) after Functional Electrical Stimulation (FES) of the Tibialis Anterior (TA) muscles. The intervention group had 10 children with spastic diaplegic/hemiplegic CP within the age group of 5 to 14 years of age who received both FES for 30 minutes and the conventional physiotherapy for 30 minutes a day, while the control group had 5 children who received only conventional physiotherapy for 60(30 + 30) minutes a day only. Both group were treated for 5 days a week, up to 12 weeks. The EEG data were analyzed for Peak Alpha Frequency (PAF), sensorimotor rhythm (SMR), mu wave suppression and power spectral density (PSD) of all the bands. The results showed a decrease in SMR and mu wave suppression in the intervention group as compared to the control group, indicating a positive/greater improvement in performance of motor activities. Therefore, from this study we could conclude that FES combined with conventional physiotherapy improves the motor activity in children with spastic CP.

  15. Solubilization of phencyclidine receptors from rat cerebral cortex in an active ligand binding site

    Energy Technology Data Exchange (ETDEWEB)

    McVittie, L.D.; Sibley, D.R.

    1989-01-01

    A phencyclidine (PCP) receptor binding site has been solubilized in an active ligand-binding state from rat cerebral cortical membranes with sodium deoxycholate. Optimal receptor solubilization occurs at a detergent/protein ratio of 0.5 (w/w); for 5 mg protein/ml solubilized with 0.25% sodium deoxycholate, about 60% of the protein and 25% of the receptor is solubilized. Specific binding of either (/sup 3/H)-N-(1-(2-thienyl)cyclohexyl)piperidine ((/sup 3/H)TCP) or (/sup 3/H)MK-801 is measurable by filtration through Sephadex G-50 columns or glass fiber filters; more than 60% of the binding activity is stable after 48 h at 4/degrees/C. In the presence of detergent, (/sup 3/H)TCP binding exhibits a K/sub d/ of 250 nM, a B/sub max/ of 0.56 pmol/mg protein, and a pharmacological profile consistent with that of the membrane-bound PCP receptor, although most drugs bind with affinities 2 to 8 fold lower than in membranes. Upon reduction of detergent concentration, binding parameters approximate those for the membrane-bound receptor (/sup 3/H)TCP binding: K/sub d/ = 48 nM, M/sub max/ = 1.13 pmol/mg protein.

  16. Differential presynaptic effects of hexachlorocyclohexane isomers on noradrenaline release in cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Cristofol, R.M.; Rodriguez-Farre, E. (Consejo Superior de Investigaciones Cientificas, Barcelona (Spain))

    1991-01-01

    To investigate presynaptic effects of hexachlorocyclohexane (HCH) isomers, the release of noradrenaline (NA) in brain tissue was analyzed using rat cerebral cortical slices preloaded with ({sup 3}H)-NA. {gamma}-HCH (lindane) 50 {mu}M significantly enhanced the ({sup 3}H)-NA release evoked by 15-25 mM K{sup +}. {alpha}- and {beta}-HCH did not produce any significant effect on K{sup +}-evoked ({sup 3}H)-NA release. {delta}-HCH induced a significant decrease of the 25 mM K{sup +}-evoked release of ({sup 3}H)-NA. The effect of the {gamma}- and {delta}-HCH isomers on the presynaptic action of the {alpha}{sub 2}-agonist clonidine and the {alpha}{sub 2}-antagonist yohimbine was also studied. The presynaptic inhibitory effect of clonidine and the stimulatory effect of yohimbine on ({sup 3}H)-NA release was attenuated by lindane and {delta}-HCH, respectively. These results are consistent with a presynaptic action of the HCH isomers on noradrenergic release processes.

  17. Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex.

    Science.gov (United States)

    Hirota, Yuki; Nakajima, Kazunori

    2017-01-01

    The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia. The extracellular protein, Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during development, plays a crucial role in the neuronal migration and neocortical lamination. Reelin signaling, which exerts essential roles in the formation of the layered neocortex, is triggered by the binding of Reelin to its receptors, ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein. Accumulating evidence suggests that Reelin signaling controls multiple steps of neuronal migration, including the transition from multipolar to bipolar neurons, terminal translocation, and termination of migration beneath the marginal zone. In addition, it has been shown that ectopically expressed Reelin can cause neuronal aggregation via an N-cadherin-mediated manner. This review attempts to summarize our knowledge of the roles played by Reelin in neuronal migration and the underlying mechanisms.

  18. Inhibition of creatine kinase activity from rat cerebral cortex by 3-hydroxykynurenine.

    Science.gov (United States)

    Cornelio, Andrea Renata; Rodrigues-Junior, Valnês da Silva; Rech, Virginia Cielo; de Souza Wyse, Angela Terezinha; Dutra-Filho, Carlos Severo; Wajner, Moacir; Wannmacher, Clovis Milton Duval

    2006-12-08

    3-hydroxykynurenine, a tryptophan metabolite, is known to be potential neurotoxic in some neurodegenerative disorders. However, the molecular mechanisms of toxicity are not well understood. Creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue. This study investigated the in vitro effect of 3-hydroxykynurenine on creatine kinase activity in the brain cortex of rats. The results indicated that low micromolar 3-hydroxykynurenine concentrations inhibit uncompetitively mitochondrial and cytosolic creatine kinase activities in a time and dose-dependent way. Inhibition was prevented, but not reversed by incubation with reduced glutathione, dithiothreitol and ascorbic acid plus trolox, suggesting adduct formation. The assay under nitrogen atmosphere suggested that the inhibition was caused by products of 3-hydroxykynurenine autoxidation. Determination of thiol groups suggested that adducts between the enzyme and autoxidation products of 3-hydroxykynurenine were not formed with sulfhydryl groups. The interaction plot between tryptophan and 3-hydroxykynurenine suggested different sites of action on creatine kinase with cross-inhibition. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity may be one of the mechanisms by which 3-hydroxykynurenine might be neurotoxic.

  19. Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

    Science.gov (United States)

    Karunamuni, Roshan A; Moore, Kevin L; Seibert, Tyler M; Li, Nan; White, Nathan S; Bartsch, Hauke; Carmona, Ruben; Marshall, Deborah; McDonald, Carrie R; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren K; Brewer, James; Dale, Anders M; Moiseenko, Vitali; Hattangadi-Gluth, Jona A

    2016-01-01

    Neurocognitive decline in brain tumor patients treated with radiotherapy (RT) may be linked to cortical atrophy. We developed models to determine radiation treatment-planning objectives for cortex, which were tested on a sample population to identify the dosimetric cost of cortical sparing. The relationship between the probability of cortical atrophy in fifteen high-grade glioma patients at 1-year post-RT and radiation dose was fit using logistic mixed effects modeling. Cortical sparing was implemented using two strategies: region-specific sparing using model parameters, and non-specific sparing of all normal brain tissue. A dose threshold of 28.6 Gy was found to result in a 20% probability of severe atrophy. Average cortical sparing at 30 Gy was greater for region-specific dose avoidance (4.6%) compared to non-specific (3.6%). Cortical sparing resulted in an increase in heterogeneity index of the planning target volume (PTV) with an average increase of 1.9% (region-specific) and 0.9% (non-specific). We found RT doses above 28.6 Gy resulted in a greater than 20% probability of cortical atrophy. Cortical sparing can be achieved using region-specific or non-specific dose avoidance strategies at the cost of an increase in the dose heterogeneity of the PTV. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

    Science.gov (United States)

    Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

  1. Motor association cortex activity in Parkinson`s disease. A functional MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Yukiko [Yamaguchi Univ., Ube (Japan). School of Medicine

    1998-08-01

    The purpose of this study was to examine the activation of motor association cortex using functional magnetic resonance imaging (fMRI) in patients with Parkinson`s disease (PD) and control subjects during performed hand movements. There were 26 patients with PD (12 patients with Hoehn and Yahr stage I-II, 14 patients with stage III) and 8 control subjects. Functional imaging was performed using a 1.5 tesla MRI system equipped with a single-shot, echo-planar pulse sequence. The significant signal changes were observed within the primary sensorimotor area, the supplementary motor area (SMA), and the parietal association area in both PD and control subjects. In PD subjects, the SMA was less activated than in control subjects; there were significant differences in the number of pixels activated in SMA between control and Yahr III group (p<0.01), and between Yahr I-II and Yahr III group (p<0.01). Our results demonstrated that movement related cerebral activity in the SMA is reduced in PD subjects, consistent with previously published data using other methods. It is well known from anatomical studies that one of the major cortical outputs of the basal ganglia is the SMA. This may explain the hypoactivation of the SMA in PD. Studies using fMRI provide a promising method not only for localizing cortical activation related to voluntary movements but also for investigating pathophysiology of movement disorders. (author)

  2. The effects of embryonic knockdown of the candidate dyslexia susceptibility gene homologue Dyx1c1 on the distribution of GABAergic neurons in the cerebral cortex.

    Science.gov (United States)

    Currier, T A; Etchegaray, M A; Haight, J L; Galaburda, A M; Rosen, G D

    2011-01-13

    Developmental dyslexia is a language-based learning disability, and a number of candidate dyslexia susceptibility genes have been identified, including DYX1C1, KIAA0319, and DCDC2. Knockdown of function by embryonic transfection of small hairpin RNA (shRNA) of rat homologues of these genes dramatically disrupts neuronal migration to the cerebral cortex by both cell autonomous and non-cell autonomous effects. Here we sought to investigate the extent of non-cell autonomous effects following in utero disruption of the candidate dyslexia susceptibility gene homolog Dyx1c1 by assessing the effects of this disruption on GABAergic neurons. We transfected the ventricular zone of embryonic day (E) 15.5 rat pups with either Dyx1c1 shRNA, DYX1C1 expression construct, both Dyx1c1 shRNA and DYX1C1 expression construct, or a scrambled version of Dyx1c1 shRNA, and sacrificed them at postnatal day 21. The mothers of these rats were injected with BrdU at either E13.5, E15.5, or E17.5. Neurons transfected with Dyx1c1 shRNA were bi-modally distributed in the cerebral cortex with one population in heterotopic locations at the white matter border and another migrating beyond their expected location in the cerebral cortex. In contrast, there was no disruption of migration following transfection with the DYX1C1 expression construct. We found untransfected GABAergic neurons (parvalbumin, calretinin, and neuropeptide Y) in the heterotopic collections of neurons in Dyx1c1 shRNA treated animals, supporting the hypothesis of non-cell autonomous effects. In contrast, we found no evidence that the position of the GABAergic neurons that made it to the cerebral cortex was disrupted by the embryonic transfection with any of the constructs. Taken together, these results support the notion that neurons within heterotopias caused by transfection with Dyx1c1 shRNA result from both cell autonomous and non-cell autonomous effects, but there is no evidence to support non-cell autonomous disruption of

  3. Factors associated with stiff knee gait in cerebral palsy

    OpenAIRE

    Compton, Eleanor Frances

    2015-01-01

    Stiff knee gait (SKG) is one of a few classified walking patterns which people with cerebral palsy (pwCP) can present with. The characteristic for SKG is delayed and/or reduced peak knee flexion during swing phase, which can reduce walking ability and result in functional restrictions. Through the use of both clinical and laboratory based measures this cross-sectional study aimed to identify the factors associated with SKG, suggest possible treatment options and propose potential directions f...

  4. Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

    Science.gov (United States)

    Peinado, Alejandro; Abrams, Charles K

    2015-01-01

    Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying

  5. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex

    Science.gov (United States)

    Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-01-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. PMID:25972586

  6. Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

    Science.gov (United States)

    Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

    2014-10-01

    The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks. © The Author (2014). Published by Oxford University Press on behalf of the

  7. Nondermatomal somatosensory deficits in chronic pain are associated with cerebral grey matter changes.

    Science.gov (United States)

    Riederer, Franz; Landmann, Gunther; Gantenbein, Andreas R; Stockinger, Lenka; Egloff, Niklaus; Sprott, Haiko; Schleinzer, Wolfgang; Pirrotta, Roberto; Dumat, Wolfgang; Luechinger, Roger; Baumgartner, Christoph; Kollias, Spyridon; Sándor, Peter S

    2017-04-01

    Widespread sensory deficits occur in 20-40% of chronic pain patients on the side of pain, independent of pain aetiology, and are known as nondermatomal sensory deficits (NDSDs). NDSDs can occur in absence of central or peripheral nervous system lesions. We hypothesised that NDSDs were associated with cerebral grey matter changes in the sensory system and in pain processing regions, detectable with voxel-based morphometry. Twenty-five patients with NDSDs, 23 patients without NDSDs ("pain-only"), and 29 healthy controls were studied with high resolution structural MRI of the brain. A comprehensive clinical and psychiatric evaluation based on Diagnostic and Statistical Manual was performed in all patients. Patients with NDSDs and "pain-only" did not differ concerning demographic data and psychiatric diagnoses, although anxiety scores (HADS-A) were higher in patients with NDSDs. In patients with NDSDs, grey matter increases were found in the right primary sensory cortex, thalamus, and bilaterally in lateral temporal regions and the hippocampus/fusiform gyrus. "Pain-only" patients showed a bilateral grey matter increase in the posterior insula and less pronounced changes in sensorimotor cortex. Dysfunctional sensory processing in patients with NDSDs is associated with complex changes in grey matter volume, involving the somatosensory system and temporal regions.

  8. Saccade abnormalities associated with focal cerebral lesions - How cortical and basal ganglia commands shape saccades in humans.

    Science.gov (United States)

    Terao, Yasuo; Fukuda, Hideki; Tokushuge, Shinnichi; Nomura, Yoshiko; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2016-08-01

    To study saccade abnormalities associated with focal cerebral lesions, including the cerebral cortex and basal ganglia (BG). We studied the latency and amplitude of reflexive and voluntary saccades in 37 patients with focal lesions of the frontal and parietal cortices and BG (caudate and putamen), and 51 age-matched controls, along with the ability to inhibit unwanted reflexive saccades. Latencies of reflexive saccades were prolonged in patients with parietal lesions involving the parietal eye field (PEF), whereas their amplitude was decreased with parietal or putaminal lesions. In contrast, latency of voluntary saccades was prolonged and their success rate reduced with frontal lesions including the frontal eye field (FEF) or its outflow tract as well as the dorsolateral/medial prefrontal cortex, and caudate lesions, whereas their amplitude was decreased with parietal lesions. Inhibitory control of reflexive saccades was impaired with frontal, caudate and, less prominently, parietal lesions. PEF is important in triggering reflexive saccades, also determining their amplitude. Whereas FEF and the caudate emit commands for initiating voluntary saccades, their amplitude is mainly determined by PEF. Commands not only from FEF and dorsolateral/medial prefrontal cortex but also from the caudate and PEF serve to inhibit unnecessary reflexive saccades. The findings suggested how cortical and BG commands shape reflexive and voluntary saccades in humans. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Spared Primary Motor Cortex and the Presence of MEP in Cerebral Palsy Dictate the Responsiveness to tDCS During Gait Training

    Directory of Open Access Journals (Sweden)

    Luanda Collange Grecco

    2016-07-01

    Full Text Available The current priority of investigations involving transcranial direct current stimulation (tDCS and neurorehabilitation is to identify biomarkers associated with the positive results of the interventions such that respondent and non-respondent patients can be identified in the early phases of treatment. The aims were to determine whether; 1 present motor evoked potential (MEP and, 2 injuries involving the primary motor cortex, are associated with tDCS-enhancement in functional outcome following gait training in children with cerebral palsy (CP. We reviewed the data from our parallel, randomized, sham-controlled, double-blind studies. Fifty-six children with spastic CP received gait training (either treadmill training or virtual reality training and tDCS (active or sham. Univariate and multivariate logistic regression analyses were employed to identify clinical, neurophysiologic and neuroanatomic predictors associated with the responsiveness to treatment with tDCS. MEP presence during the initial evaluation and the subcortical injury were associated with positive effects in the functional results. The logistic regression revealed that present MEP was a significant predictor for the six-minute walk test (p=0.003 and gait speed (p=0.028, whereas the subcortical injury was a significant predictor of gait kinematics (p=0.013 and gross motor function (p = 0.021. In this preliminary study involving children with CP, two important prediction factors of good responses to anodal tDCS combined with gait training were identified. Apparently, MEP (integrity of the corticospinal tract and subcortical location of the brain injury exerted different influences on aspects related to gait, such as velocity and kinematics.

  10. Differential binding of /sup 3/H-imipramine and /sup 3/H-mianserin in rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Dumbrille-Ross, A.; Tang, S.W.; Coscina, D.V.

    1981-11-16

    Drug competition profiles, effect of raphe lesion, and sodium dependency of the binding of two antidepressant drugs /sup 3/H-imipramine and /sup 3/H-mianserin to rat cerebral cortex homogenate were compared to examine whether the drugs bound to a common ''antidepressant receptor.'' Of the neurotransmitters tested, only serotonin displaced binding of both /sup 3/H-imipramine and /sup 3/H-mianserin. /sup 3/H-Mianserin binding was potently displaced by serotonin S/sub 2/ antagonists and exhibited a profile similar to that of /sup 3/H-spiperone binding. In the presence of the serotonin S/sub 2/ antagonist spiperone, antihistamines (H/sub 1/) potently displaced /sup 3/H-mianserin binding. /sup 3/H-Imipramine binding was displaced potently by serotonin uptake inhibitors. The order of potency of serotonergic drugs in displacing /sup 3/H-imipramine binding was not similar to their order in displacing /sup 3/H-spiperone or -3H-serotonin binding. Prior midbrain raphe lesions greatly decreased the binding of /sup 3/H-imipramine but did not alter binding of /sup 3/H-mianserin. Binding of /sup 3/H-imipramine but not /sup 3/H-mianserin was sodium dependent. These results show that /sup 3/H-imipramine and /sup 3/H-mianserin bind to different receptors. /sup 3/H-Imipramine binds to a presynaptic serotonin receptor which is probably related to a serotonin uptake recognition site, the binding of which is sodium dependent. /sup 3/H-Mianserin binds to postsynaptic receptors, possibly both serotonin S/sub 2/ and histamine H/sub 1/ receptors, the binding of which is sodium independent.

  11. Impact of Neuronal Membrane Damage on the Local Field Potential in a Large-Scale Simulation of Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    David L. Boothe

    2017-06-01

    Full Text Available Within multiscale brain dynamics, the structure–function relationship between cellular changes at a lower scale and coordinated oscillations at a higher scale is not well understood. This relationship may be particularly relevant for understanding functional impairments after a mild traumatic brain injury (mTBI when current neuroimaging methods do not reveal morphological changes to the brain common in moderate to severe TBI such as diffuse axonal injury or gray matter lesions. Here, we created a physiology-based model of cerebral cortex using a publicly released modeling framework (GEneral NEural SImulation System to explore the possibility that performance deficits characteristic of blast-induced mTBI may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level. We operationalized microscale damage to neurons as the formation of pores on the neuronal membrane based on research using blast paradigms, and in our model, pores were simulated by a change in membrane conductance. We then tracked changes in simulated electrical activity. Our model contained 585 simulated neurons, comprised of 14 types of cortical and thalamic neurons each with its own compartmental morphology and electrophysiological properties. Comparing the functional activity of neurons before and after simulated damage, we found that simulated pores in the membrane reduced both action potential generation and local field potential (LFP power in the 1–40 Hz range of the power spectrum. Furthermore, the location of damage modulated the strength of these effects: pore formation on simulated axons reduced LFP power more strongly than did pore formation on the soma and the dendrites. These results indicate that even small amounts of cellular damage can negatively impact functional activity of larger scale oscillations, and our findings suggest that multiscale modeling provides a promising avenue to elucidate these relationships.

  12. The effects of kinesio taping on potential in chronic low back pain patients anticipatory postural control and cerebral cortex.

    Science.gov (United States)

    Bae, Sea Hyun; Lee, Jeong Hun; Oh, Kyeong Ae; Kim, Kyung Yoon

    2013-11-01

    [Purpose] This study aimed to examine the effects of kinesio tape applied to chronic low back pain (CLBP) patients on anticipatory postural control and cerebral cortex potential. [Subjects and Methods] Twenty patients whose low back pain had continued for more than 12 weeks were selected and assigned to a control group (n=10) to which ordinary physical therapy was applied and an experimental group (n=10) to which kinesio tape was applied. Anticipatory postural control was evaluated using electromyography, and movement-related cortical potential (MRCP) was assessed using electroencephalography. Clinical evaluation was performed using a visual analogue scale and the Oswestry disability index. [Results] According to the analysis results for anticipatory postural control, there were significant decreases in the transversus abdominis (TrA) muscle and the external oblique muscle in both groups. Among them, the TrA of the experimental group exhibited the greatest differences. According to the results of a between-group comparison, there was significant difference in the TrA between the two groups. There was also a significant decrease in the MRCP of both groups. In particular, changes in the movement monitoring potential (MMP) of the experimental group were greatest at Fz, C3, Cz, and C4. According to the between-group comparison, there were significant differences in MMP at F3, C3, and Cz. Both groups saw VAS and ODI significantly decrease. Among them, the ODI of the experimental group underwent the greatest change. [Conclusion] Kinesio tape applied to CLBP patients reduced their pain and positively affected their anticipatory postural control and MRCP.

  13. Affinity chromatography of alpha/sub 2/-adrenergic receptors (. cap alpha. /sub 2/AR) from pig cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Repaske, M.G.; Limbird, L.E.

    1986-03-01

    A high capacity, ..cap alpha../sub 2/AR-selective affinity resin (YOH. ag) has been prepared by coupling yohimbinic acid to diaminodipropylamine agarose with 1,3 dicyclohexylcarbodiimide. Unreacted amino groups on the agarose matrix are blocked subsequently by acetylation. One volume of YOH. ag adsorbs 75% of the ..cap alpha../sub 2/AR from 50 volumes of digitonin-solubilized preparation containing 0.2 pmol ..cap alpha../sub 2/AR/mg protein. Digitonin-solubilized preparations are derived from cholate extracts of porcine cerebral cortex containing approx. 0.075 pmol ..cap alpha../sub 2/AR/mg protein. Adsorption of ..cap alpha../sub 2/AR to YOH. ag is selective and thus is blocked by the ..cap alpha..-adrenergic antagonist phentolamine. Adsorbed ..cap alpha../sub 2/AR are eluted with 10 ..mu..M phentolamine (20% yield) after removal of non-related proteins with NaCl gradients. Following hydroxylapatite chromatography to concentrate ..cap alpha..''AR and to remove phentolamine, the ..cap alpha..AR is present at 200-400 pmol/mg protein, assayed using sub-saturating concentrations of (/sup 3/H)-yohimbine. (It is estimated that the specific activity of a homogeneous ..cap alpha../sub 2/AR preparation would be 12,000-16,000 pmol/mg protein.) The availability of large quantities of cortical ..cap alpha../sub 2/AR and a resin easily prepared from commercially-supplied reagents suggests that purification of quantities of ..cap alpha../sub 2/AR sufficient for subsequent biochemical studies is feasible.

  14. Using individualized brain network for analyzing structural covariance of the cerebral cortex in Alzheimer’s patients

    Directory of Open Access Journals (Sweden)

    Hee-Jong Kim

    2016-09-01

    Full Text Available Cortical thinning patterns in Alzheimer’s disease (AD have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are small world. There were significant difference between NC and AD group in characteristic path lengths (z=-2.97, p<0.01 and small-worldness values (z=4.05, p<0.01. Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z=1.81, not significant. We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI data to show consistency in results with the SMC

  15. Impact of Neuronal Membrane Damage on the Local Field Potential in a Large-Scale Simulation of Cerebral Cortex.

    Science.gov (United States)

    Boothe, David L; Yu, Alfred B; Kudela, Pawel; Anderson, William S; Vettel, Jean M; Franaszczuk, Piotr J

    2017-01-01

    Within multiscale brain dynamics, the structure-function relationship between cellular changes at a lower scale and coordinated oscillations at a higher scale is not well understood. This relationship may be particularly relevant for understanding functional impairments after a mild traumatic brain injury (mTBI) when current neuroimaging methods do not reveal morphological changes to the brain common in moderate to severe TBI such as diffuse axonal injury or gray matter lesions. Here, we created a physiology-based model of cerebral cortex using a publicly released modeling framework (GEneral NEural SImulation System) to explore the possibility that performance deficits characteristic of blast-induced mTBI may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level. We operationalized microscale damage to neurons as the formation of pores on the neuronal membrane based on research using blast paradigms, and in our model, pores were simulated by a change in membrane conductance. We then tracked changes in simulated electrical activity. Our model contained 585 simulated neurons, comprised of 14 types of cortical and thalamic neurons each with its own compartmental morphology and electrophysiological properties. Comparing the functional activity of neurons before and after simulated damage, we found that simulated pores in the membrane reduced both action potential generation and local field potential (LFP) power in the 1-40 Hz range of the power spectrum. Furthermore, the location of damage modulated the strength of these effects: pore formation on simulated axons reduced LFP power more strongly than did pore formation on the soma and the dendrites. These results indicate that even small amounts of cellular damage can negatively impact functional activity of larger scale oscillations, and our findings suggest that multiscale modeling provides a promising avenue to elucidate these relationships.

  16. LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome.

    Directory of Open Access Journals (Sweden)

    Ayumi Matsumoto

    Full Text Available Interstitial deletion of 12q21 has been reported in four cases, which share several common clinical features, including intellectual disability (ID, low-set ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH analysis using the Agilent Human Genome CGH 180K array was performed with the genomic DNA from a two-year-old Japanese boy with these symptoms, as well as hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2-q21.33 (nt. 77 203 574-91 264 613 bp, which includes 72 genes, was detected. Of these, we focused on LIN7A, which encodes a scaffold protein that is important for synaptic function, as a possible responsible gene for ID, and we analyzed its role in cerebral cortex development. Western blotting analyses revealed that Lin-7A is expressed on embryonic day (E 13.5, and gradually increases in the mouse brain during the embryonic stage. Biochemical fractionation resulted in the enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A expression by RNAi, using in utero electroporation on E14.5, delayed neuronal migration on postnatal day (P 2, and Lin-7A-deficient neurons remained in the lower zone of the cortical plate and the intermediate zone. In addition, when Lin-7A was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed; development of these neurons was disrupted such that one half did not extend into the contralateral hemisphere after leaving the corpus callosum. Taken together, LIN7A is a candidate gene responsible for 12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric axon development may contribute to ID and corpus callosum hypoplasia, respectively.

  17. LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome.

    Science.gov (United States)

    Matsumoto, Ayumi; Mizuno, Makoto; Hamada, Nanako; Nozaki, Yasuyuki; Jimbo, Eriko F; Momoi, Mariko Y; Nagata, Koh-ichi; Yamagata, Takanori

    2014-01-01

    Interstitial deletion of 12q21 has been reported in four cases, which share several common clinical features, including intellectual disability (ID), low-set ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH) analysis using the Agilent Human Genome CGH 180K array was performed with the genomic DNA from a two-year-old Japanese boy with these symptoms, as well as hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2-q21.33 (nt. 77 203 574-91 264 613 bp), which includes 72 genes, was detected. Of these, we focused on LIN7A, which encodes a scaffold protein that is important for synaptic function, as a possible responsible gene for ID, and we analyzed its role in cerebral cortex development. Western blotting analyses revealed that Lin-7A is expressed on embryonic day (E) 13.5, and gradually increases in the mouse brain during the embryonic stage. Biochemical fractionation resulted in the enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A expression by RNAi, using in utero electroporation on E14.5, delayed neuronal migration on postnatal day (P) 2, and Lin-7A-deficient neurons remained in the lower zone of the cortical plate and the intermediate zone. In addition, when Lin-7A was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed; development of these neurons was disrupted such that one half did not extend into the contralateral hemisphere after leaving the corpus callosum. Taken together, LIN7A is a candidate gene responsible for 12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric axon development may contribute to ID and corpus callosum hypoplasia, respectively.

  18. Cerebral magnetic resonance changes associated with fibromyalgia syndrome.

    Science.gov (United States)

    Murga, Iñigo; Guillen, Virginia; Lafuente, José-Vicente

    2017-06-07

    Fibromyalgia syndrome is a chronic disease, of unknown origin, whose diagnostic criteria were established in 1990 by the American College of Rheumatology. New criteria were proposed in 2010 that have not yet been validated. It is characterized by a generalized chronic musculoskeletal pain, accompanied by hyperalgesia and allodynia, as well as other motor, vegetative, cognitive and affective symptoms and signs. We have reviewed a set of studies with cerebral magnetic resonance (morphometry, connectivity and spectroscopy) that refer to changes in areas involved in pain processing. Modifications in gray and white matter volume, as well as in levels of N-acetylaspartate, choline or glutamate, among other metabolites, have been observed in the hippocampus, insula, prefrontal and cingular cortex. Neuroradiological findings are nonspecific and similar to those found in other examples of chronic pain. An increase in the sample size and a standardized methodology would facilitate comparison, allowing the drawing of general conclusions. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Mutations in Gamma Adducin are Associated With Inherited Cerebral Palsy

    Science.gov (United States)

    Kruer, Michael C; Jepperson, Tyler; Dutta, Sudeshna; Steiner, Robert D; Cottenie, Ellen; Sanford, Lynn; Merkens, Mark; Russman, Barry S; Blasco, Peter A; Fan, Guang; Pollock, Jeffrey; Green, Sarah; Woltjer, Randall L; Mooney, Catherine; Kretzschmar, Doris; Paisán-Ruiz, Coro; Houlden, Henry

    2013-01-01

    Objective Cerebral palsy is estimated to affect nearly 1 in 500 children, and although prenatal and perinatal contributors have been well characterized, at least 20% of cases are believed to be inherited. Previous studies have identified mutations in the actin-capping protein KANK1 and the adaptor protein-4 complex in forms of inherited cerebral palsy, suggesting a role for components of the dynamic cytoskeleton in the genesis of the disease. Methods We studied a multiplex consanguineous Jordanian family by homozygosity mapping and exome sequencing, then used patient-derived fibroblasts to examine functional consequences of the mutation we identified in vitro. We subsequently studied the effects of adducin loss of function in Drosophila. Results We identified a homozygous c.1100G>A (p.G367D) mutation in ADD3, encoding gamma adducin in all affected members of the index family. Follow-up experiments in patient fibroblasts found that the p.G367D mutation, which occurs within the putative oligomerization critical region, impairs the ability of gamma adducin to associate with the alpha subunit. This mutation impairs the normal actin-capping function of adducin, leading to both abnormal proliferation and migration in cultured patient fibroblasts. Loss of function studies of the Drosophila adducin ortholog hts confirmed a critical role for adducin in locomotion. Interpretation Although likely a rare cause of cerebral palsy, our findings indicate a critical role for adducins in regulating the activity of the actin cytoskeleton, suggesting that impaired adducin function may lead to neuromotor impairment and further implicating abnormalities of the dynamic cytoskeleton as a pathogenic mechanism contributing to cerebral palsy. PMID:23836506

  20. Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Leke, Renata; Escobar, Thayssa D.C.; Rama Rao, Kakulavarapu V.

    2015-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE. Under physiologica...... that the expression of the glutamine transporter isoforms is unchanged during chronic HE, and thus likely not to participate in the pathological mechanisms related to the imbalance in the GABAergic neurotransmitter system observed in this neurologic condition.......Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE. Under physiological...... conditions, glutamine is fundamental for replenishment of the neurotransmitter pools of glutamate and GABA. The different isoforms of glutamine transporters play an important role in the transfer of this amino acid between astrocytes and neurons. A disturbance in the GABA biosynthetic pathways has been...

  1. Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex

    DEFF Research Database (Denmark)

    Walløe, Solveig; Pakkenberg, Bente; Fabricius, Katrine

    2014-01-01

    Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct...... brain cell populations, and disease-related changes associated with a loss of function. In that this article concerns normal brain rather than brain disorders, it focuses on normal brain development in humans and age related changes in terms of cell numbers. For comparative purposes a few examples...... estimates and were often very time-consuming. Within the last 20-30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected...

  2. Comparison of auditory deficits associated with neglect and auditory cortex lesions.

    Science.gov (United States)

    Gutschalk, Alexander; Brandt, Tobias; Bartsch, Andreas; Jansen, Claudia

    2012-04-01

    In contrast to lesions of the visual and somatosensory cortex, lesions of the auditory cortex are not associated with self-evident contralesional deficits. Only when two or more stimuli are presented simultaneously to the left and right, contralesional extinction has been observed after unilateral lesions of the auditory cortex. Because auditory extinction is also considered a sign of neglect, clinical separation of auditory neglect from deficits caused by lesions of the auditory cortex is challenging. Here, we directly compared a number of tests previously used for either auditory-cortex lesions or neglect in 29 controls and 27 patients suffering from unilateral auditory-cortex lesions, neglect, or both. The results showed that a dichotic-speech test revealed similar amounts of extinction for both auditory cortex lesions and neglect. Similar results were obtained for words lateralized by inter-aural time differences. Consistent extinction after auditory cortex lesions was also observed in a dichotic detection task. Neglect patients showed more general problems with target detection but no consistent extinction in the dichotic detection task. In contrast, auditory lateralization perception was biased toward the right in neglect but showed considerably less disruption by auditory cortex lesions. Lateralization of auditory-evoked magnetic fields in auditory cortex was highly correlated with extinction in the dichotic target-detection task. Moreover, activity in the right primary auditory cortex was somewhat reduced in neglect patients. The results confirm that auditory extinction is observed with lesions of the auditory cortex and auditory neglect. A distinction can nevertheless be made with dichotic target-detection tasks, auditory-lateralization perception, and magnetoencephalography. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Regional cerebral blood flow changes associated with clitorally induced orgasm in healthy women.

    Science.gov (United States)

    Georgiadis, Janniko R; Kortekaas, Rudie; Kuipers, Rutger; Nieuwenburg, Arie; Pruim, Jan; Reinders, A A T Simone; Holstege, Gert

    2006-12-01

    There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [15O]-H2O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state, clitorally induced orgasm, sexual clitoral stimulation (sexual arousal control) and imitation of orgasm (motor output control). Extracerebral markers of sexual performance and orgasm were rectal pressure variability (RPstd) and perceived level of sexual arousal (PSA). Sexual stimulation of the clitoris (compared to rest) significantly increased rCBF in the left secondary and right dorsal primary somatosensory cortex, providing the first account of neocortical processing of sexual clitoral information. In contrast, orgasm was mainly associated with profound rCBF decreases in the neocortex when compared with the control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus and anterior temporal pole. Significant positive correlations were found between RPstd and rCBF in the left deep cerebellar nuclei, and between PSA and rCBF in the ventral midbrain and right caudate nucleus. We propose that decreased blood flow in the left lateral orbitofrontal cortex signifies behavioural disinhibition during orgasm in women, and that deactivation of the temporal lobe is directly related to high sexual arousal. In addition, the deep cerebellar nuclei may be involved in orgasm-specific muscle contractions while the involvement of the ventral midbrain and right caudate nucleus suggests a role for dopamine in female sexual arousal and orgasm.

  4. Multicenter assessment of morbidity associated with cerebral arteriovenous malformation hemorrhages.

    Science.gov (United States)

    Fukuda, Keiko; Majumdar, Monica; Masoud, Hesham; Nguyen, Thanh; Honarmand, Amir; Shaibani, Ali; Ansari, Sameer; Tan, Lee A; Chen, Michael

    2017-07-01

    The optimal management strategy for unruptured cerebral arteriovenous malformations (AVMs) is controversial since the ARUBA trial (A Randomized trial of Unruptured Brain AVMs). An accurate understanding of the morbidity associated with AVM hemorrhages may help clinicians to formulate the best treatment strategy for unruptured AVMs. To determine the morbidity associated with initial cerebral AVM rupture in patients presenting to tertiary medical centers. Retrospective chart reviews from three tertiary academic medical centers were performed for the period between 2008 and 2014. All patients admitted with intracranial hemorrhage due to untreated AVMs were included in this study. Patient-specific variables, including demographics, imaging characteristics, neurologic examination results, and clinical outcome, were analyzed and recorded. 101 Patients met the inclusion criteria. Admission National Institutes of Health Stroke Scale (NIHSS) scores were 0, 1-9, and ≥10 in 26%, 29%, and 45% of patients, respectively. Hematoma locations were subarachnoid, intraventricular, intraparenchymal, and combined in 5%, 11%, 32%, and 52% of patients, respectively. Deep venous drainage was present in 43% of AVMs; AVM-associated aneurysms were present in 44% of patients. Emergent hematoma evacuations were performed in 37% of patients and 8% of patients died while in hospital. At discharge, of those who survived, NIHSS scores of ≥1 and ≥10 were found in 69% and 23%, respectively. At the 90-day follow-up, 34% had a modified Rankin Scale (mRS) score >2. Patients with admission NIHSS score ≥10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥3 (pmorbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment

  5. l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

    Science.gov (United States)

    Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

    2017-01-01

    We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats.

    Science.gov (United States)

    Viegas, C M; Zanatta, Â; Grings, M; Hickmann, F H; Monteiro, W O; Soares, L E; Sitta, Â; Leipnitz, G; de Oliveira, F H; Wajner, M

    2014-06-01

    Hyperammonemia is a common finding in children with methylmalonic acidemia and propionic acidemia, but its contribution to the development of the neurological symptoms in the affected patients is poorly known. Considering that methylmalonic acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders, we investigated the effects of hyperammonemia induced by urease treatment in 30-day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on important parameters of redox homeostasis in cerebral cortex and striatum. We evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and nitrite concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, and the activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl content and increased nitrate and nitrite concentrations in cerebral cortex and striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter these parameters. MMA plus hyperammonemia also decreased glutathione reductase activity in rat cerebral cortex, but did not affect catalase, superoxide dismutase and glutathione peroxidase activities, neither DCFH oxidation. Furthermore, ICV PA administration alone or combined with hyperammonemia did not alter any of the evaluated parameters. We also found that pre-treatment with antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas N(ω)-nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and nitrite concentrations provoked by MMA plus ammonia treatments. Histological alterations, including vacuolization, ischemic neurons, and pericellular edema, were observed in brain of hyperammonemic rats injected with MMA. The data indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and causing morphological brain abnormalities in rat brain.

  7. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species.

    Science.gov (United States)

    Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M; de Castro Leal, Maria E; Bertelsen, Mads F; Alagaili, Abdulaziz N; Mohammad, Osama B; Manger, Paul R; Herculano-Houzel, Suzana

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran

  8. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Science.gov (United States)

    Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M.; de Castro Leal, Maria E.; Bertelsen, Mads F.; Alagaili, Abdulaziz N.; Mohammad, Osama B.; Manger, Paul R.; Herculano-Houzel, Suzana

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran

  9. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Directory of Open Access Journals (Sweden)

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  10. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  11. PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.

    Science.gov (United States)

    Fast, Rikke; Rodell, Anders; Gjedde, Albert; Mouridsen, Kim; Alstrup, Aage K; Bjarkam, Carsten R; West, Mark J; Berendt, Mette; Møller, Arne

    2013-01-01

    Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aβ) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aβ and cognitive decline in animal models of cognitive decline is of interest to the understanding of AD. However, the sensitivity of the biomarker Pittsburgh Compound B (PiB) to the presence of Aβ in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aβ in dog brain, we mapped the brains of dogs with signs of CCD (n = 16) and a control group (n = 4) of healthy dogs with radioactively labeled PiB ([(11)C]PiB). Structural magnetic resonance imaging brain scans were obtained from each dog. Tracer washout analysis yielded parametric maps of PiB retention in brain. In the CCD group, dogs had significant retention of [(11)C]PiB in the cerebellum, compared to the cerebral cortex. Retention in the cerebellum is at variance with evidence from brains of humans with AD. To confirm the lack of sensitivity, we stained two dog brains with the immunohistochemical marker 6E10, which is sensitive to the presence of both Aβ and Aβ precursor protein (AβPP). The 6E10 stain revealed intracellular material positive for Aβ or AβPP, or both, in Purkinje cells. The brains of the two groups of dogs did not have significantly different patterns of [(11)C]PiB binding, suggesting that the material detected with 6E10 is AβPP rather than Aβ. As the comparison with the histological images revealed no correlation between the [(11)C]PiB and Aβ and AβPP deposits in post-mortem brain, the marked intracellular staining implies intracellular involvement of amyloid processing in the dog brain. We conclude that PET maps of [(11)C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.

  12. Cerebral sinovenous thrombosis associated with iron deficiency anemia secondary to severe menorrhagia: a case report.

    Science.gov (United States)

    Corrales-Medina, Fernando F; Grant, Leon; Egas-Bejar, Daniela; Valdivia-Ascuna, Zoila; Rodriguez, Nidra; Mancias, Pedro

    2014-09-01

    Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed. © The Author(s) 2013.

  13. The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex.

    Science.gov (United States)

    Herbet, Mariola; Szopa, Aleksandra; Wosko, Sylwia; Serefko, Anna; Izdebska, Magdalena; Gawronska-Grzywacz, Monika; Piatkowska-Chmiel, Iwona; Janas, Martyna; Gieroba, Renata; Korga, Agnieszka; Poleszak, Ewa; Dudka, Jaroslaw

    2017-01-01

    Depressive disorders are associated with oxidative stress. Therefore, it is interesting if antidepressants can affect redox equilibrium and signaling. The first step of our study was to determine the influence of the adenosine system on the antidepressant-like activity of noncompetitive antagonist of the NMDA (N-methyl-d-aspartate) receptor complex - dizocilpine (MK- 801). To this aim, two behavioral tests commonly used to assess the antidepressant capability of drugs - the forced swim test (FST) and tail suspension test (TST), were performed. Locomotor activity was estimated to verify and exclude false positive/negative results in the FST and TST. To examine whether antidepressants affect redox equilibrium, we have investigated lipid peroxidation products (LPO), GSH (glutathione), GSSG (glutathione disulfide), NADP+ (nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate) in the cerebral cortex of mice following administration of CPT (8-cyclopentyl-1,3-dimethylxanthine) and MK-801 (dizocilpine) under environmental stress conditions. The experiments were carried out using male Albino Swiss mice (25-30 g). The drugs were administered ip., alone and simultaneously, 60 min before tests. The behavioural tests results showed that CPT (3 mg/kg) potentiated the antidepressant-like activity of MK-801 (0.05 mg/kg) and the observed effects were not due to the increase in mice locomotor activity. Positive synergism of CPT and MK-801 in reduction of environmental stress conditions was revealed. In this group an increase in GSH and GSSG without changes in GSH/GSSG ratio and reduction of LPO was found. The level of lipid peroxidation products was also decreased in group receiving CPT and MK-801 separately. Examined antidepressant agents may increase antioxidant defences however further studies are needed with different range of time. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Association between cerebral hemodynamic changes and neonatal hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    LIU Shuyan

    2017-10-01

    Full Text Available ObjectiveTo investigate the association between cerebral hemodynamic changes and neonatal hyperbilirubinemia. MethodsA total of 67 neonates with hyperbilirubinemia who were admitted to our hospital from January 2014 to November 2015 were enrolled as study group, and another 36 normal healthy neonates were enrolled as control group. The two groups were compared in terms of end-diastolic velocity (Vd, systolic peak velocity (Vs, mean blood flow velocity (Vm, resistance index (RI, and pulsatility index (PI, and the serum level of bilirubin and systemic symptoms were observed after treatment. The t-test was used for comparison of continuous data between groups, and a Pearson correlation analysis was also performed. ResultsAt the time of enrolment and on day 3 of treatment, the control group had significantly lower Vd, Vs, and Vm than the study group (before treatment: t=75873,81589,64600,19834,30453; day 3 of treatment: t=39476,55729,35274,6069,9382, all P<0.001. The study group had improvements in Vd, Vs, Vm, RI, and PI on day 3 of treatment. On day 5 of treatment, there were no significant differences in hemodynamic parameters between the two groups (all P>0.05. Serum level of bilirubin was positively correlated with Vd (r=0.387, P<0.001, Vs (r=0.483, P<0.001, and Vm (r=0.412, P<0.001 and negatively correlated with RI (r=-0.492, P<0.001 and PI (r=-0.497, P<0.001. ConclusionSerum level of bilirubin interacts with cerebral hemodynamics, and cerebral hemodynamic parameters can provide objective evidence for evaluating disease progression and prognosis of neonatal hyperbilirubinemia.

  15. The Association of Cerebral Palsy with Other Disability in Children with Perinatal Arterial Ischemic Stroke

    OpenAIRE

    Golomb, Meredith R.; Saha, Chandan; Garg, Bhuwan P.; Azzouz, Faouzi; Williams, Linda S.

    2007-01-01

    The association of cerebral palsy with other disability in children with perinatal stroke has not been well-studied. We examined this association in 111 children with perinatal stroke, 67 with neonatal presentation and 44 with delayed presentation. Seventy-six children (68%) had cerebral palsy, which was hemiplegic in 66 and tri- or quadriplegic in 10. Fifty-five (72%) of the children with cerebral palsy had at least one other disability: 45 (59%) had cognitive/speech impairment which was mod...

  16. Subcellular Changes in Bridging Integrator 1 Protein Expression in the Cerebral Cortex During the Progression of Alzheimer Disease Pathology.

    Science.gov (United States)

    Adams, Stephanie L; Tilton, Kathy; Kozubek, James A; Seshadri, Sudha; Delalle, Ivana

    2016-08-01

    Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate-to-marked AD pathology, who had been assessed by Clinical Dementia Rating and CERAD scores. We also examined the amygdala, prefrontal, temporal, and occipital regions in a subset of these patients. In non-demented controls without AD pathology, BIN1 protein was expressed in white matter, glia, particularly oligodendrocytes, and in the neuropil in which the BIN1 signal decorated axons. With increasing severity of AD, BIN1 in the CA1 region showed: 1) sustained expression in glial cells, 2) decreased areas of neuropil expression, and 3) increased cytoplasmic neuronal expression that did not correlate with neurofibrillary tangle load. In patients with AD, both the prefrontal cortex and CA1 showed a decrease in BIN1-immunoreactive (BIN1-ir) neuropil areas and increases in numbers of BIN1-ir neurons. The numbers of CA1 BIN1-ir pyramidal neurons correlated with hippocampal CERAD neuritic plaque scores; BIN1 neuropil signal was absent in neuritic plaques. Our data provide novel insight into the relationship between BIN1 protein expression and the progression of AD-associated pathology and its diagnostic hallmarks. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  17. Ethanol withdrawal increases glutathione adducts of 4-hydroxy-2-hexenal but not 4-hydroxyl-2-nonenal in the rat cerebral cortex.

    Science.gov (United States)

    Long, Eric K; Rosenberger, Thad A; Picklo, Matthew J

    2010-02-01

    Ethanol withdrawal increases lipid peroxidation of the polyunsaturated fatty acid (PUFA) docosahexaenoate (22:6; n-3) in the CNS. To further define the role of oxidative damage of PUFAs during ethanol withdrawal, we measured the levels of glutathione adducts of 4-hydroxy-2-hexenal (GSHHE) and 4-hydroxy-2-nonenal (GSHNE) as biomarkers of brain lipid peroxidation of n-3 and n-6 PUFAs, respectively. In this study rats received an ethanol-containing diet for 6 weeks followed by withdrawal ranging from 0 to 7 days. GSHHE content was elevated (>350%) in the cerebral cortex after 2 days of withdrawal with no change in GSHNE. The levels of GSHHE were significantly greater (2- to 20-fold) than those of GSHNE in multiple brain regions. Experiments demonstrated that intoxication and withdrawal did not alter the enzymatic rate of formation of GSHHE or GSHNE, but the rate of formation of GSHHE was higher (approximately 50%) than that of GSHNE. These results indicate that selective oxidative damage to n-3 PUFAs occurs in the cerebral cortex as a result of ethanol withdrawal and that 4-hydroxy-2-hexenal is metabolized to the GSH adduct more efficiently than HNE. Copyright 2009. Published by Elsevier Inc.

  18. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Niara da Silva Medeiros

    2015-01-01

    Full Text Available Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS, protein oxidation (carbonyl, sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

  19. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats.

    Science.gov (United States)

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

  20. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

    Science.gov (United States)

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings. PMID:26649198

  1. Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

    Directory of Open Access Journals (Sweden)

    Ming-Kuei eLu

    2012-09-01

    Full Text Available The cerebellum is crucially important for motor control and motor adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and motor adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP-like modifications of motor cortex (M1 excitability by application of paired associative stimulation (PAS in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB preceded focal TMS of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS2ms, 6 ms (CB→M1 PAS6ms or 10 ms (CB→M1 PAS10ms or randomly alternating intervals of 2 and 10 ms (CB→M1 PASControl. Effects of PAS on M1 excitability were assessed by the motor evoked potential (MEP amplitude, short-interval intracortical inhibition (SICI, intracortical facilitation (ICF and cerebellar-motor cortex inhibition (CBI in the first dorsal interosseous muscle of the right hand. CB→M1 PAS2ms resulted in MEP potentiation, CB→M1 PAS6ms and CB→M1 PAS10ms in MEP depression, and CB→M1 PASControl in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity.

  2. Migraine with visual aura associated with thicker visual cortex

    DEFF Research Database (Denmark)

    Gaist, David; Hougaard, Anders; Garde, Ellen

    2018-01-01

    Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura...... the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a thicker cortex corresponding to visual areas and our...

  3. Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

    Science.gov (United States)

    Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

    1990-01-01

    Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

  4. Expression of glucose transporter-1 and aquaporin-4 in the cerebral cortex of stroke-prone spontaneously hypertensive rats in relation to the blood-brain barrier function.

    Science.gov (United States)

    Ishida, Hiroyuki; Takemori, Kumiko; Dote, Kensaku; Ito, Hiroyuki

    2006-01-01

    Cerebral edema is an important initial event in cases of stroke among humans. Although hypertension is a major risk factor for endothelial injury, the precise mechanisms regulating brain microvascular changes are still unknown. To elucidate the pathogenesis of increases in vascular permeability in the cerebral cortex, we investigated the expression of glucose transporter-1 (GLUT-1) in endothelial cells and aquaporin-4 (AQP4) in astrocytes in relation to blood-brain barrier (BBB) function. Using male stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY), the particular localization of both GLUT-1 and AQP4 was investigated by immunohistochemistry. Quantitative changes in these molecules were examined by Western blot analysis in these rats at 6 weeks and 20 weeks of age. Furthermore, to investigate the expression of these molecules at the mRNA level, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was carried out using 20-week-old SHRSP and age-matched WKY. We confirmed the localization of GLUT-1 in endothelial cells and that of AQP4 in the end feet of astrocytes around microvessels, as determined by electron immunohistochemistry. No significant differences were found in the expression of these molecules in rats at 6 weeks of age, whereas GLUT-1 expression was lower, but that of AQP4 was higher, in SHRSP after the establishment of hypertension. Furthermore, GLUT-1 mRNA expression was lower in SHRSP, and AQP4 mRNA expression was also lower in SHRSP than in WKY at 20 weeks of age. These results indicate that AQP4 may play a much more important role in BBB function than GLUT-1, and thereby also in water distribution in the cerebral cortex of SHRSP with severe hypertension.

  5. Dopamine D sub 2 receptors in the cerebral cortex: Distribution and pharmacological characterization with ( sup 3 H)raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Lidow, M.S.; Goldman-Rakic, P.S.; Rakic, P.; Innis, R.B. (Yale Univ., New Haven, CT (USA))

    1989-08-01

    An apparent involvement of dopamine in the regulation of cognitive functions and the recognition of a widespread dopaminergic innervation of the cortex have focused attention on the identity of cortical dopamine receptors. However, only the presence and distribution of dopamine D{sub 1} receptors in the cortex have been well documented. Comparable information on cortical D{sub 2} sites is lacking. The authors report here the results of binding studied in the cortex and neostriatum of rat and monkey using the D{sub 2} selective antagonist ({sup 3}H)raclopride. In both structures ({sup 3}H)raclopride bound in a sodium-dependent and saturable manner to a single population of sites with pharmacological profiles of dopamine D{sub 2} receptors. D{sub 2} sites were present in all regions of the cortex, although their density was much lower than in the neostriatum. The density of these sites in both monkey and, to a lesser extent, rat cortex displayed a rostral-caudal gradient with highest concentrations in the prefrontal and lowest concentrations in the occipital cortex, corresponding to dopamine levels in these areas. Thus, the present study established the presence and widespread distribution of dopamine D{sub 2} receptors in the cortex.

  6. Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex.

    Science.gov (United States)

    Villa, Roberto Federico; Gorini, Antonella; Hoyer, Siegfried

    2009-12-01

    The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

  7. Retinotopic Changes in the Gray Matter Volume and Cerebral Blood Flow in the Primary Visual Cortex of Patients With Primary Open-Angle Glaucoma.

    Science.gov (United States)

    Zhang, Shaodan; Wang, Bo; Xie, Yuan; Zhu, SenHua; Thomas, Ravi; Qing, Guoping; Zhang, Chun; Wang, Ningli

    2015-09-01

    To assess the cortical structure and cerebral blood flow changes in the brain of patients with primary open-angle glaucoma (POAG). High-resolution anatomical magnetic resonance imaging (MRI) and arterial spin labeling (ASL)-MRI were performed in 23 POAG patients and 29 controls. Patients were further divided into early-moderate and advanced groups based on mean deviation (MD) cutoff of 12 dB. A baseline scan was obtained and repeated during visual stimulation to the central preserved visual field in the more affected eye of POAG patients and a randomly selected eye of controls. Gray matter volume (GMV) and cerebral blood flow (CBF) throughout the whole brain were compared between patients and controls. Compared to controls, a region with significant reduction of GMV was detected in the anterior calcarine fissure of advanced POAG patients (P Primary open-angle glaucoma patients demonstrate a disease severity-dependent retinotopic pattern of cortical atrophy and CBF abnormalities in the visual cortex. Cerebral blood flow may be a potential biomarker for the brain involvement in glaucoma.

  8. Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Ujjwal K. Rout

    2010-11-01

    Full Text Available Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS. Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

  9. Liquid-diet with alcohol alters maternal, fetal and placental weights and the expression of molecules involved in integrin signaling in the fetal cerebral cortex.

    Science.gov (United States)

    Rout, Ujjwal K; Dhossche, Julie M

    2010-11-01

    Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β(1) and α(3) integrin subunits and phospholipase-Cγ(2) were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

  10. Administration of vitamin D 3 induces CNPase and myelin oligodendrocyte glycoprotein expression in the cerebral cortex of the murine model of cuprizone-induced demyelination

    Directory of Open Access Journals (Sweden)

    Farhad Mashayekhi

    2016-10-01

    Full Text Available In the central nervous system (CNS the main proteins of myelin are proteolipid protein (PLP, myelin basic protein (MBP, myelin oligodendrocyte glycoprotein (MOG and CNPase. Myelin oligodendrocyte glycoprotein is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of multiple sclerosis (MS. CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation and myelination. In this study the effects of vitamin D on total protein concentration, CNPase and MOG expression in the cerebral cortex of the murine model of cuprizone-induced demyelination was investigated. The mice were treated by cuprizone for five weeks in order to induce demyelination. The mice were then divided into 3 groups. The first group was injected intraperitoneally (IP with vitamin D diluted in olive oil in the amount of 5 µg/kg/daily body weight. The second group (SHAM was injected IP with olive oil and the third group was left without any injection as the control group (n = 11 for each group. After five weeks the mice were killed and the cerebral cortex was collected and the expression of CNPase and MOG was studied by Western blot. Total protein concentration in the vitamin D injected, SHAM and control groups were 0.918 ± 0.003, 0917 ± 0.004 and 0.916 ± 0.004 g/l, respectively (p > 0.05. However, a significant increase in the MOG and CNPase expression was seen in vitamin D injected group as compared to SHAM and control groups. It is concluded that vitamin D plays a role in the process of remyelination by increasing MOG and CNPase expression in the cortex.

  11. Association between Apolipoprotein E genotype and cerebral palsy is not confirmed in a Caucasian population.

    Science.gov (United States)

    McMichael, Gai L; Gibson, Catherine S; Goldwater, Paul N; Haan, Eric A; Priest, Kevin; Dekker, Gustaaf A; MacLennan, Alastair H

    2008-11-01

    Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with prenatal viral infection to influence risk of cerebral palsy. The population-based case-control study comprised newborn screening cards of 443 Caucasian patients with cerebral palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA extracted from dried blood spots. Allelic and genotypic frequencies did not differ between cases and controls and combined frequencies were 0.10 (epsilon2), 0.76 (epsilon3), 0.14 (epsilon4), 0.03 (epsilon2/epsilon2), 0.10 (epsilon2/epsilon3), 0.03 (epsilon2/epsilon4), 0.02 (epsilon4/epsilon4), 0.21 (epsilon3/epsilon4), 0.61 (epsilon3/epsilon3). APOE genotype was correlated with cerebral palsy, type of cerebral palsy, gestation at birth and the presence of viral nucleic acids detected in previous work. Analysis by gestational age (all gestational ages, >/=37, 32-36 and <32 weeks) and type of cerebral palsy (all types, diplegia, hemiplegia and quadriplegia) showed no association between APOE genotype and cerebral palsy in this Caucasian population. An association between prenatal viral infection, APOE genotype and cerebral palsy was not demonstrated. These results did not confirm an association between APOE genotype, cerebral palsy, type of cerebral palsy and prenatal infection in a Caucasian population. Given the low frequency of APOE epsilon2 and some of the heterozygote and homozygote combinations in this study, a larger study is assessing this further.

  12. In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

    Science.gov (United States)

    Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

    2017-05-01

    Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The steady-state response of the cerebral cortex to the beat of music reflects both the comprehension of music and attention.

    Science.gov (United States)

    Meltzer, Benjamin; Reichenbach, Chagit S; Braiman, Chananel; Schiff, Nicholas D; Hudspeth, A J; Reichenbach, Tobias

    2015-01-01

    The brain's analyses of speech and music share a range of neural resources and mechanisms. Music displays a temporal structure of complexity similar to that of speech, unfolds over comparable timescales, and elicits cognitive demands in tasks involving comprehension and attention. During speech processing, synchronized neural activity of the cerebral cortex in the delta and theta frequency bands tracks the envelope of a speech signal, and this neural activity is modulated by high-level cortical functions such as speech comprehension and attention. It remains unclear, however, whether the cortex also responds to the natural rhythmic structure of music and how the response, if present, is influenced by higher cognitive processes. Here we employ electroencephalography to show that the cortex responds to the beat of music and that this steady-state response reflects musical comprehension and attention. We show that the cortical response to the beat is weaker when subjects listen to a familiar tune than when they listen to an unfamiliar, non-sensical musical piece. Furthermore, we show that in a task of intermodal attention there is a larger neural response at the beat frequency when subjects attend to a musical stimulus than when they ignore the auditory signal and instead focus on a visual one. Our findings may be applied in clinical assessments of auditory processing and music cognition as well as in the construction of auditory brain-machine interfaces.

  14. Effect of Transcranial Direct Current Stimulation over the Primary Motor Cortex on Cerebral Blood Flow: A Time Course Study Using Near-infrared Spectroscopy.

    Science.gov (United States)

    Takai, Haruna; Tsubaki, Atsuhiro; Sugawara, Kazuhiro; Miyaguchi, Shota; Oyanagi, Keiichi; Matsumoto, Takuya; Onishi, Hideaki; Yamamoto, Noriaki

    2016-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that is applied during stroke rehabilitation. The purpose of this study was to examine diachronic intracranial hemodynamic changes using near-infrared spectroscopy (NIRS) during tDCS applied to the primary motor cortex (M1). Seven healthy volunteers were tested during real stimulation (anodal and cathodal) and during sham stimulation. Stimulation lasted 20 min and NIRS data were collected for about 23 min including the baseline. NIRS probe holders were positioned over the entire contralateral sensory motor area. Compared to the sham condition, both anodal and cathodal stimulation resulted in significantly lower oxyhemoglobin (O2Hb) concentrations in the contralateral premotor cortex (PMC), supplementary motor area (SMA), and M1 (pstimulation was significantly lower than that during the sham condition (pstimulation was lower than that during anodal stimulation (pstimulation was significantly higher than the concentrations during both cathodal stimulation and the sham condition (p<0.05). The factor of time did not demonstrate significant differences. These results suggest that both anodal and cathodal tDCS cause widespread changes in cerebral blood flow, not only in the area immediately under the electrode, but also in other areas of the cortex.

  15. Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice

    Science.gov (United States)

    Urban, Alan; Rancillac, Armelle; Martinez, Lucie; Rossier, Jean

    2012-01-01

    Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF. PMID:22715327

  16. Nerve cell nuclear and nucleolar abnormalities in the human oedematous cerebral cortex. An electron microscopic study using cortical biopsies.

    Science.gov (United States)

    Castejón, O J; Arismendi, G J

    2004-01-01

    Cerebral cortical biopsies of 17 patients with clinical diagnosis of congenital hydrocephalus, complicated brain trauma, cerebellar syndrome and vascular anomaly were examined with the transmission electron microscope to study the nuclear and nucleolar abnormalities induced by moderate and severe brain oedema, and the associated anoxic-ischemic conditions of brain tissue. In infant patients with congenital hydrocephalus and Arnold-Chiari malformation two different structural patterns of immature chromatin organization were found: the clear type characterized by a clear granular and fibrillar structure of euchromatin, scarce heterochromatin masses and few perichromatin granules, and a dense granular and fibrillar euchromatin with abundant and scattered heterochromatin masses, and increased number of perichromatin granules. The lobulated nuclei exhibited an irregularly dilated and fragmented perinuclear cistern, and areas of apparently intact nuclear pore complexes alternating with regions of nuclear pore complex disassembly. In moderate traumatic brain injuries some nucleoli exhibit apparent intact nucleolar substructures, and in severe brain oedema some nucleoli appeared shrunken and irregularly outlined with one or two fibrillar centers, and others were disintegrated. The nuclear and nucleolar morphological alterations are discussed in relation with oxidative stress, peroxidative damage, hemoglobin-induced cytotoxicity, calcium overload, glutamate excitotoxicity, and caspase activation.

  17. Effects of cerebro-protective agents on enzyme activities of rat primary glial cultures and rat cerebral cortex.

    Science.gov (United States)

    Bielenberg, G W; Hayn, C; Krieglstein, J

    1986-08-15

    The effects of different cerebro-protective agents on selected key enzymes of the energy metabolism of rat primary glial cultures and rat cerebral cortex were studied. As indicators for the capacity of the most important pathways of energy metabolism the following enzyme activities were determined: hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-P-DH), malate dehydrogenase (MDH), glutamate dehydrogenase (GDH), and cytochrome-c-reductase (CCR). After a one week growth period, rat glial cultures were incubated for 3 or 4 weeks with the substances to be tested. Bencyclane (5 X 10(-5) mol/l) increased the activities of HK, G-6-P-DH, and LDH, whereas PFK and CCR were reduced. Pyritinol (10(-4) mol/l) led to a higher G-6-P-DH activity, simultaneously lowering the values for PFK, CCR, PK, LDH, and MDH. Under the influence of an extract of the leaves of Ginkgo bilobae (EGB; 100 mg/l) PFK, LDH, and MDH activities were reduced. All these alterations in enzyme activities went along with simultaneous reductions in protein content, therefore not allowing to exclude toxic effects with regard to the doses used. Moreover, direct interference with the analytical procedure was demonstrable for bencyclane and EGB. Piracetam (10(-3) mol/l), flunarizine (10(-6) mol/l), dihydroergocristine (5 X 10(-6) mol/l), and nicergoline (5 X 10(-6) mol/l) failed to induce any alteration in the employed doses. The most striking effects were obtained with meclofenoxate which was tested at 10(-3) and 10(-4) mol/l. The higher dose caused an elevation of HK, PFK, CCR, G-6-P-DH, GDH and MDH activities, while slightly reducing PK. With the lower dose of meclofenoxate CCR and G-6-P-DH activities were increased. Short-term incubation of the cultures with 10(-3) mol/l meclofenoxate for 24 hr led to an increase in LDH, G-6-P-DH, and GDH activities. Chronic incubation with meclofenoxate (10(-3) mol/l) followed by 48 hr

  18. Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Schreckenberger, M.; Sabri, O.; Arning, C.; Schulz, G.; Tuttass, T.; Wagenknecht, G.; Kaiser, H.J.; Buell, U. [Department of Nuclear Medicine, Aachen University of Technology, Aachen (Germany); Gouzoulis-Mayfrank, E.; Sass, H. [Department of Psychiatry, Aachen University of Technology, Aachen (Germany)

    1998-11-01

    Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca`s area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional

  19. Bilateral cerebral hemispheric infarction associated with sildenafil citrate (Viagra) use.

    Science.gov (United States)

    Kim, K-K; Kim, D G; Ku, Y H; Lee, Y J; Kim, W-C; Kim, O J; Kim, H S

    2008-03-01

    Sildenafil citrate (Viagra) is one of the frequently prescribed drugs for men with erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil and about 1 h later, he complained of chest discomfort, palpitation and dizziness followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic resonance imaging documented acute bilateral hemispheric infarction, and cerebral angiography showed occluded bilateral MCA. Despite significant bilateral MCA stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume that cerebral infarction was caused by cardioembolism with sildenafil use.

  20. Bundle of measures for external cerebral ventricular drainage-associated ventriculitis.

    Science.gov (United States)

    Chatzi, Maria; Karvouniaris, Marios; Makris, Demosthenes; Tsimitrea, Eleni; Gatos, Charalampos; Tasiou, Anastasia; Mantzarlis, Kostas; Fountas, Kostas N; Zakynthinos, Epaminondas

    2014-01-01

    To assess the prevalence and outcome of external cerebral ventricular drainage-associated ventriculitis in neurocritical patients before and after the implementation of a bundle of external cerebral ventricular drainage-associated ventriculitis control measures. Clinical prospective case series. University Hospital of Larissa, Greece. Consecutive patients were recruited from the ICU of the hospital. Patient inclusion criteria included presence of external ventricular drainage and ICU stay more than 48 hours. The bundle of external cerebral ventricular drainage-associated ventriculitis control measures included 1) reeducation of ICU personnel on issues of infection control related to external cerebral ventricular drainage, 2) meticulous intraventricular catheter handling, 3) cerebrospinal fluid sampling only when clinically necessary, and 4) routine replacement of the drainage catheter on the seventh drainage day if the catheter was still necessary. The bundle was applied after an initial period (preintervention) where standard policy for external cerebral ventricular drainage-associated ventriculitis was established. External cerebral ventricular drainage-associated ventriculitis prevalence, external cerebral ventricular drainage-associated ventriculitis events per 1,000 drainage days (drain-associated infection rate), length of ICU stay, Glasgow Outcome Scale at 6 months, and risk factors for external cerebral ventricular drainage-associated ventriculitis. Eighty-two patients entered the study in the preintervention period and 57 patients during the intervention period. During the preintervention and intervention period, external cerebral ventricular drainage-associated ventriculitis prevalence was 28% and 10.5% (p = 0.02) and drain-associated infection rate was 18 and 7.1, respectively (p = 0.0001); mean (95% CI) length of ICU stay in patients who presented external cerebral ventricular drainage-associated ventriculitis was 44.4 days (36.4-52.4 d), whereas mean

  1. Spatiotemporal Profiles of Proprioception Processed by the Masseter Muscle Spindles in Rat Cerebral Cortex: An Optical Imaging Study.

    Science.gov (United States)

    Fujita, Satoshi; Kaneko, Mari; Nakamura, Hiroko; Kobayashi, Masayuki

    2017-01-01

    Muscle spindles in the jaw-closing muscles, which are innervated by trigeminal mesencephalic neurons (MesV neurons), control the strength of occlusion and the position of the mandible. The mechanisms underlying cortical processing of proprioceptive information are critical to understanding how sensory information from the masticatory muscles regulates orofacial motor function. However, these mechanisms are mostly unknown. The present study aimed to identify the regions that process proprioception of the jaw-closing muscles using in vivo optical imaging with a voltage-sensitive dye in rats under urethane anesthesia. First, jaw opening that was produced by mechanically pulling down the mandible evoked an optical response, which reflects neural excitation, in two cortical regions: the most rostroventral part of the primary somatosensory cortex (S1) and the border between the ventral part of the secondary somatosensory cortex (S2) and the insular oral region (IOR). The kinetics of the optical signal, including the latency, amplitude, rise time, decay time and half duration, in the S1 region for the response with the largest amplitude were comparable to those in the region with the largest response in S2/IOR. Second, we visualized the regions responding to electrical stimulation of the masseter nerve, which activates both motor efferent fibers and somatosensory afferent fibers, including those that transmit nociceptive and proprioceptive information. Masseter nerve stimulation initially excited the rostral part of the S2/IOR region, and an adjacent region responded to jaw opening. The caudal part of the region showing the maximum response overlapped with the region responding to jaw opening, whereas the rostral part overlapped with the region responding to electrical stimulation of the maxillary and mandibular molar pulps. These findings suggest that proprioception of the masseter is processed in S1 and S2/IOR. Other sensory information, such as nociception, is

  2. Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral Cortex in the Presence or Absence of Nitric Oxide Inhibition.

    Science.gov (United States)

    Yarube, I U; Ayo, J O; Fatihu, M Y; Magaji, R A; Umar, I A; Alhassan, A W; Saleh, M Ia

    2017-03-06

    Insulin has emerged from its traditional 'peripheral' glucose-lowering function to become increasingly regarded as a brain hormone that controls a wide range of functions including learning and memory. Insulin action on learning and memory is linked to nitric oxide (NO) signalling, but its effects on memory and histology of cerebral cortex in conditions of varied NO availability is unclear. This research sought to determine the effect of insulin on visuo-spatial learning, memory and histology of cerebral cortex during NO deficiency. Twenty-four mice weighing 21-23 g, were divided into four groups (n = 6) and treated daily for seven days with 0.2 ml distilled water subcutaneously (s.c.) (control), 10 I.U/kg insulin s.c., 10 I.U/kg insulin + 50 mg/kg L-NAME intraperitoneally (i.p.), and 50 mg/kg i.p. L-NAME s.c., respectively. The 3-day MWM paradigm was used to assess memory. Brain tissue was examined for histological changes. There was no significant difference between day 1 and day 2 latencies for all the groups. The mice in all (but L-NAME) groups spent more time in the target quadrant, and the difference was significant within but not between groups. There was significant reduction in number of platform site crossings (4.83 ± 0.5, 0.67 ± 0.3, 0.50 ± 0.3 and 0.50 ± 0.3 for control, insulin, insulin+L-NAME and L-NAME groups, respectively) in all the groups compared to control. Normal histology of the cortex and absence of histological lesions were observed in brain slides of control and treatment groups. It was concluded that insulin administration impairs visuo-spatial memory to a greater extent in the presence of NO block, and to a lesser extent in the absence of NO block. Nitric oxide has a role in insulin-induced memory impairment. Insulin administration in the presence or absence of NO block had no effect on histology of cortex.

  3. Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

    Directory of Open Access Journals (Sweden)

    Saba Pierluigi

    2005-05-01

    Full Text Available Abstract Background Previous studies by our group suggest that extracellular dopamine (DA and noradrenaline (NA may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC. This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC, occipital cortex (Occ, and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT blocker desipramine (DMI, 100 μM, multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant

  4. Simultaneous Electroencephalography, Real-time Measurement of Lactate Concentration and Optogenetic Manipulation of Neuronal Activity in the Rodent Cerebral Cortex

    OpenAIRE

    Clegern, William C.; Moore, Michele E.; Schmidt, Michelle A.; Wisor, Jonathan

    2012-01-01

    Although the brain represents less than 5% of the body by mass, it utilizes approximately one quarter of the glucose used by the body at rest1. The function of non rapid eye movement sleep (NREMS), the largest portion of sleep by time, is uncertain. However, one salient feature of NREMS is a significant reduction in the rate of cerebral glucose utilization relative to wakefulness2-4. This and other findings have led to the widely held belief that sleep serves a function related to cerebral me...

  5. Angiopoietin-1 is associated with cerebral vasospasm and delayed cerebral ischemia in subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Pfausler Bettina

    2011-05-01

    Full Text Available Abstract Background Angiopoietin-1 (Ang-1 and -2 (Ang-2 are keyplayers in the regulation of endothelial homeostasis and vascular proliferation. Angiopoietins may play an important role in the pathophysiology of cerebral vasospasm (CVS. Ang-1 and Ang-2 have not been investigated in this regard so far. Methods 20 patients with subarachnoid hemorrhage (SAH and 20 healthy controls (HC were included in this prospective study. Blood samples were collected from days 1 to 7 and every other day thereafter. Ang-1 and Ang-2 were measured in serum samples using commercially available enzyme-linked immunosorbent assay. Transcranial Doppler sonography was performed to monitor the occurrence of cerebral vasospasm. Results SAH patients showed a significant drop of Ang-1 levels on day 2 and 3 post SAH compared to baseline and HC. Patients, who developed Doppler sonographic CVS, showed significantly lower levels of Ang-1 with a sustained decrease in contrast to patients without Doppler sonographic CVS, whose Ang-1 levels recovered in the later course of the disease. In patients developing cerebral ischemia attributable to vasospasm significantly lower Ang-1 levels have already been observed on the day of admission. Differences of Ang-2 between SAH patients and HC or patients with and without Doppler sonographic CVS were not statistically significant. Conclusions Ang-1, but not Ang-2, is significantly altered in patients suffering from SAH and especially in those experiencing CVS and cerebral ischemia. The loss of vascular integrity, regulated by Ang-1, might be in part responsible for the development of cerebral vasospasm and subsequent cerebral ischemia.

  6. Neurochemical changes in the hippocampus and prefrontal cortex associated with electroacupuncture for learning and memory impairment.

    Science.gov (United States)

    He, Jian; Zhao, Congkuai; Liu, Weilin; Huang, Jia; Liang, Shengxiang; Chen, Lidian; Tao, Jing

    2018-02-01

    Electroacupuncture (EA) has been widely used to treat cognitive impairment following cerebral ischemia. However, the functional mechanisms of EA have not been fully elucidated. The aim of the present study was to investigate whether EA at the GV 20 and DU 24 acupoints can improve the learning and memory ability via alteration of the neurochemical metabolism in the hippocampus (HPC) and prefrontal cortex (PFC) of rats with ischemia and reperfusion (I/R) injury. Sprague‑Dawley male rats were randomly divided into three groups, namely the sham group (n=12), the middle cerebral artery occlusion (MCAO) group (n=12) and the EA treatment (MCAO + EA) group (n=12). MCAO was performed to establish the left focal cerebral I/R injury model, and the GV 20 and DU 24 acupoints were then stimulated with EA for 30 min per time, once daily, for 7 consecutive days. The Morris water maze (MWM) test was used to assess learning and memory ability. T2‑weighted imaging was used to assess the cerebral infarct volume. Magnetic resonance spectroscopy was used to assess neurochemical metabolism of HPC and PFC. The neurological scores of the MCAO + EA group were significantly reduced compared with those of the MCAO group 7 days after EA treatment (Pplatform area was significantly higher in the MCAO + EA group compared with that in the MCAO group (P0.05). The ratios of NAA/Cr, Cho/Cr and Glu/Cr of left‑to‑right PFC were elevated (Plearning and memory ability, possibly through increasing the levels of NAA and Cho in the HPC and PFC of rats with I/R injury.

  7. Characterization of the fiber connectivity profile of the cerebral cortex in schizotypal personality disorder: A pilot study

    Directory of Open Access Journals (Sweden)

    Kai eLiu

    2016-05-01

    Full Text Available Schizotypal personality disorder (SPD is considered one of the classic disconnection syndromes. However, the specific cortical disconnectivity pattern has not been fully investigated. In this study, we aimed to explore significant alterations in whole-cortex structural connectivity in SPD individuals (SPDs by combining the techniques of brain surface morphometry and white matter (WM tractography. Diffusion and structural MR data were collected from twenty subjects with SPD (all males; age, 19.7 ± 0.9 yrs and eighteen healthy controls (all males; age, 20.3 ± 1.0 yrs. To measure the structural connectivity for a given unit area of the cortex, the fiber connectivity density (FiCD value was proposed and calculated as the sum of the fractional anisotropy of all the fibers connecting to that unit area in tractography. Then, the resultant whole-cortex FiCD maps were compared in a vertex-wise manner between SPDs and controls. Compared with normal controls, SPDs showed significantly decreased FiCD in the rostral middle frontal gyrus (crossing BA9 and BA10 and significantly increased FiCD in the anterior part of the fusiform/inferior temporal cortex (P < 0.05, Monte Carlo simulation corrected. Moreover, the gray matter volume extracted from the left rostral middle frontal cluster was observed to be significantly greater in the SPD group (P = 0.02. Overall, this study identifies a decrease in connectivity in the left middle frontal cortex as a key neural deficit at the whole-cortex level in SPD, thus providing insight into its neuropathological basis.

  8. The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

    Science.gov (United States)

    Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

    2013-01-01

    The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID

  9. The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

    Directory of Open Access Journals (Sweden)

    Pedro F. M. Ribeiro

    2013-09-01

    Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

  10. Anti-neuroinflammatory and antioxidant effects of N-acetyl cysteine in long-term consumption of artificial sweetener aspartame in the rat cerebral cortex

    Directory of Open Access Journals (Sweden)

    Afaf Abbass Sayed Saleh

    2015-10-01

    Long term consumption of the artificial sweetener aspartame (ASP induced large increments in cortical inflammation and oxidative stress. Daily oral NAC administration can significantly reverse brain-derived neurotrophic factor (BDNF levels, blocked the cyclooxygenase-2 (COX-2 and prostaglandin E2 (PGE2 production with selective attenuation in expression of proinflammatory cytokines of interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α in the rat cerebral cortex. Also, NAC can significantly replenish and correct intracellular glutathione (GSH levels, modulate the elevated levels of total nitric oxide (TNO and lipid peroxidation (LPO. Conclusions: The present results amply support the concept that the brain oxidative stress and inflammation coexist in experimental animals chronically treated with aspartame and they represent two distinct therapeutic targets in ASP toxicity. The present data propose that NAC attenuated ASP neurotoxicity and improved neurological functions, suppressed brain inflammation, and oxidative stress responses and may be a useful strategy for treating ASP-induced neurotoxicity.

  11. Frozen fruit pulp of Euterpe oleraceae Mart. (Acai) prevents hydrogen peroxide-induced damage in the cerebral cortex, cerebellum, and hippocampus of rats.

    Science.gov (United States)

    Spada, Patricia D S; Dani, Caroline; Bortolini, Giovana V; Funchal, Claudia; Henriques, João A P; Salvador, Mirian

    2009-10-01

    Oxidative stress is implicated in several human illnesses, including neurological disorders such as Parkinson's and Alzheimer's diseases. Acai is largely consumed in Brazil and contains high levels of antioxidant compounds. This work aims to study the antioxidant activity of acai frozen fruit pulp in the cerebral cortex, hippocampus, and cerebellum of rats treated with the oxidizing agent hydrogen peroxide (H(2)O(2)). Pretreatment of tissue with acai decreased H(2)O(2)-induced damage of both lipids and proteins in all tissues tested. This fruit was also able to reduce the activities of the antioxidant enzymes superoxide dismutase and catalase to basal levels. We observed a negative correlation between the polyphenol content of acai and the levels of lipid (r = -0.689; P data suggest that acai has a positive contribution in the development of age-related neurodegenerative diseases.

  12. Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane.

    Directory of Open Access Journals (Sweden)

    Michelle J Porritt

    Full Text Available Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2 and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p. after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.

  13. Photothrombosis-Induced Infarction of the Mouse Cerebral Cortex Is Not Affected by the Nrf2-Activator Sulforaphane

    Science.gov (United States)

    Hou, Linda; Nilsson, Åsa; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

    2012-01-01

    Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage. PMID:22911746

  14. Effects of Vision Restoration Training on Early Visual Cortex in Patients With Cerebral Blindness Investigated With Functional Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Raemaekers, M.; Bergsma, D.P.; van Wezel, Richard Jack Anton; van der Wildt, G.J.; van den Berg, A.V.

    Cerebral blindness is a loss of vision as a result of postchiasmatic damage to the visual pathways. Parts of the lost visual field can be restored through training. However, the neuronal mechanisms through which training effects occur are still unclear. We therefore assessed training-induced changes

  15. Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Chuu, Jiunn-Jye; Huang, Zih-Ning; Yu, Hsun-Hsin; Chang, Liang-Hao [College of Engineering, Southern Taiwan University, Institute of Biotechnology, Tainan (China); Lin-Shiau, Shoei-Yn [College of Medicine, National Taiwan University, Institute of Pharmacology, Taipei (China)

    2008-06-15

    This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease of Na{sup +}/K{sup +}-ATPase and Ca{sup 2+}-ATPase activities. Furthermore, NO levels of blood but not that of cerebral cortex were also decreased by mercuric compounds. Although pentobarbital alone enhanced cytochrome p450-2C9 in time dependent manner, all of mercurial compounds tested had no such effect. All of these findings indicated that the mercurial compounds including cinnabar, HgS and MeHg exert a long-lasting enhancing hypnotic activity without affecting pentobarbital metabolism, which provides evidence-based sedative effect of cinnabar used in Chinese traditional medicine for more than 2,000 years. The nontoxic HgS dosing (0.1 g/kg/day) for consecutive 7 days is perhaps useful for delaying or preventing pentobarbital-tolerance. (orig.)

  16. The Role of the Parietal Cortex in the Representation of Task-Reward Associations.

    Science.gov (United States)

    Wisniewski, David; Reverberi, Carlo; Momennejad, Ida; Kahnt, Thorsten; Haynes, John-Dylan

    2015-09-09

    Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors and their outcomes. Much previous work focused on how rewards affect the processing of specific tasks. However, abstract associations between multiple potential behaviors and multiple rewards are an important basis for adaptation as well. In this experiment, we directly investigated which brain areas represent associations between multiple tasks and rewards, using time-resolved multivariate pattern analysis of functional magnetic resonance imaging data. Importantly, we were able to dissociate neural signals reflecting task-reward associations from those related to task preparation and reward expectation processes, variables that were often correlated in previous research. We hypothesized that brain regions involved in processing tasks and/or rewards will be involved in processing associations between them. Candidate areas included the dorsal anterior cingulate cortex, which is involved in associating simple actions and rewards, and the parietal cortex, which has been shown to represent task rules and action values. Our results indicate that local spatial activation patterns in the inferior parietal cortex indeed represent task-reward associations. Interestingly, the parietal cortex flexibly changes its content of representation within trials. It first represents task-reward associations, later switching to process tasks and rewards directly. These findings highlight the importance of the inferior parietal cortex in associating behaviors with their outcomes and further show that it can flexibly reconfigure its function within single trials. Significance statement: Rewards obtained from specific behaviors rarely remain constant over time. To adapt to changing conditions, humans need to continuously update and represent the current association between behavior and its outcomes. However, little is known

  17. Random or selective neuroanatomical connectivity. Study of the distribution of fibers over two populations of identified interneurons in cerebral cortex

    NARCIS (Netherlands)

    Vinkenoog, M.; van den Oever, M.C.; Uylings, H.B.M.; Wouterlood, F.G.

    2005-01-01

    We present a neuroanatomical tracing method in a stereological approach to study the proportional distribution of fibers of a particular projection over two chemically different populations of neurons. The fiber projection from the presubiculum to the medial division of the entorhinal cortex of the

  18. Evaluation of cerebral activity in the prefrontal cortex in mood [affective] disorders during animal-assisted therapy (AAT) by near-infrared spectroscopy (NIRS): a pilot study.

    Science.gov (United States)

    Aoki, Jun; Iwahashi, Kazuhiko; Ishigooka, Jun; Fukamauchi, Fumihiko; Numajiri, Maki; Ohtani, Nobuyo; Ohta, Mitsuaki

    2012-09-01

    Previous studies have shown the possibility that animal-assisted therapy (AAT) is useful for promoting the recovery of a patient's psychological, social, and physiological aspect. As a pilot study, we measured the effect that AAT had on cerebral activity using near-infrared spectroscopy (NIRS), and examined whether or not NIRS be used to evaluate the effect of AAT biologically and objectively. Two patients with mood [affective] disorders and a healthy subject participated in this study. We performed two AAT and the verbal fluency task (VFT). The NIRS signal during AAT showed great [oxy-Hb] increases in most of the prefrontal cortex (PFC) in the two patients. When the NIRS pattern during AAT was compared with that during VFT, greater or lesser differences were observed between them in all subjects. The present study suggested that AAT possibly causes biological and physiological changes in the PFC, and that AAT is useful for inducing the activity of the PFC in patients with depression who have generally been said to exhibit low cerebral activity in the PFC. In addition, the possibility was also suggested that the effect of AAT can be evaluated using NIRS physiologically and objectively.

  19. Neuroanatomical correlates of personality in chimpanzees (Pan troglodytes): Associations between personality and frontal cortex.

    Science.gov (United States)

    Latzman, Robert D; Hecht, Lisa K; Freeman, Hani D; Schapiro, Steven J; Hopkins, William D

    2015-12-01

    Converging empirical data suggests that a set of largely consistent personality traits exist in both human and nonhuman primates; despite these similarities, almost nothing is known concerning the neurobiological basis of these traits in nonhuman primates. The current study examined associations between chimpanzee personality traits and the grey matter volume and asymmetry of various frontal cortex regions in 107 captive chimpanzees. Chimpanzees rated as higher on Openness and Extraversion had greater bilateral grey matter volumes in the anterior cingulate cortex. Further, chimpanzee rated as higher on Dominance had larger grey volumes in the left anterior cingulate cortex and right Prefrontal Cortex (PFC). Finally, apes rated higher on Reactivity/Unpredictability had higher grey matter volumes in the right mesial PFC. All associations survived after applying False Discovery Rate (FDR) thresholds. Results are discussed in terms of current neuroscientific models of personality which suggest that the frontal cortex, and asymmetries in this region, play an important role in the neurobiological foundation of broad dispositional traits. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Dendritic arborization patterns of interneurons labeled with a lectin, Vicia villosa, in rat cerebral cortex: studies by intracellular injection of lucifer yellow using aldehyde-fixed slices].

    Science.gov (United States)

    Ojima, H

    1993-04-01

    In order to characterize the dendritic field of a number of interneurons in the cerebral cortex, the labeling of extracellular sugar chains which define a subset of interneurons was combined with the subsequent intracellular filling of dyes in aldehyde-fixed tissue. Neurons whose cell body had been outlined by a lectin, Vicia villosa (VVA), which recognizes terminal N-acetylgalactosamine, were intracellularly injected with a fluorescent tracer, Lucifer yellow (LY), in the rat parietal cortex under direct visualization. After immunohistochemical detection of LY, somal morphology and the dendritic fields of injected neurons were reconstructed from serial sections and characterized in each of the layers II/III, IV, V and VI. Multipolar, flask-shaped and bitufted somata were VVA-positive. Multipolar neurons with round soma and spherical dendritic field were found in layers II/III, IV and V, while those with vertically elongated dendritic fields were found in layer VI. Cell bodies were located roughly in the center of the spherical or cylindrical dendritic fields. Neurons with apparently multipolar but flask- or pear-shaped soma were found frequently in layer IV, and much less frequently in layer II/III and VI. The majority of the dendrites originated from the neck portion of flask and formed a roughly spherical dendritic field with the cell body located more or less eccentrically. Some neurons in layer IV had an oval, somewhat vertically elongated soma and displayed a typical bitufted dendritic arborization pattern with vertically elongated dendritic fields. The overall dendritic field sizes of the cells gradually increased at deeper layers of the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion

    Directory of Open Access Journals (Sweden)

    Gianfranca Carta

    2018-01-01

    Full Text Available This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R and to investigate RVT’s ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle, while the second half received the vehicle alone. In the frontal cortex, RVT pre-treatment prevented the BCCAO/R-induced increase of lipoperoxides, augmented concentrations of palmitoylethanolamide and docosahexaenoic acid, increased relative levels of the cannabinoid receptors type 1 (CB1 and 2 (CB2, and peroxisome-proliferator-activated-receptor (PPAR-α proteins. Increased expression of CB1/CB2 receptors mirrored that of synaptophysin and post-synaptic density-95 protein. No BCCAO/R-induced changes occurred in the temporal-occipital cortex. Collectively, our results demonstrate that, in the frontal cortex, RVT pre-treatment prevents the BCCAO/R-induced oxidative stress and modulates the endocannabinoid and PPAR-α systems. The increased expression of synaptic structural proteins further suggests the possible efficacy of RVT as a dietary supplement to preserve the nervous tissue metabolism and control the physiological response to the hypoperfusion/reperfusion challenge.

  2. LONG-TERM HOMEOSTASIS OF EXTRACELLULAR GLUTAMATE IN THE RAT CEREBRAL CORTEX ACROSS SLEEP AND WAKING STATES

    OpenAIRE

    Dash, Michael B; Douglas, Christopher L.; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Tononi, Giulio

    2009-01-01

    Neuronal firing patterns, neuromodulators, and cerebral metabolism change across sleep waking states, and the synaptic release of glutamate is critically involved in these processes. Extrasynaptic glutamate can also affect neural function and may be neurotoxic, but whether and how extracellular glutamate is regulated across sleep-waking states is unclear. To assess the effect of behavioral state on extracellular glutamate at high temporal resolution, we recorded glutamate concentration in pre...

  3. Imaging cerebral tryptophan metabolism in brain tumor-associated depression.

    Science.gov (United States)

    Bosnyák, Edit; Kamson, David O; Behen, Michael E; Barger, Geoffrey R; Mittal, Sandeep; Juhász, Csaba

    2015-12-01

    Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[(11)C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD', an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. The mean BDI-II score was 12 ± 10 (range: 2-33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p Tumor size, grade, and tumor type were not related to depression scores. Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of

  4. Clinical Spectrum of Cerebral Palsy and Associated Disability in South Egypt: A Local Survey Study

    Directory of Open Access Journals (Sweden)

    Osama Abas

    2017-02-01

    CONCLUSION: Cerebral palsy in developing countries has a higher prevalence and different clinical profile regarding severity and associated disability. The perinatal and high-quality neonatal care together with physical therapy and rehabilitation programs is still lacking in developing countries.

  5. Associative Recognition Memory Awareness Improved by Theta-Burst Stimulation of Frontopolar Cortex.

    Science.gov (United States)

    Ryals, Anthony J; Rogers, Lynn M; Gross, Evan Z; Polnaszek, Kelly L; Voss, Joel L

    2016-03-01

    Neuroimaging and lesion studies have implicated specific prefrontal cortex locations in subjective memory awareness. Based on this evidence, a rostrocaudal organization has been proposed whereby increasingly anterior prefrontal regions are increasingly involved in memory awareness. We used theta-burst transcranial magnetic stimulation (TBS) to temporarily modulate dorsolateral versus frontopolar prefrontal cortex to test for distinct causal roles in memory awareness. In three sessions, participants received TBS bilaterally to frontopolar cortex, dorsolateral prefrontal cortex, or a control location prior to performing an associative-recognition task involving judgments of memory awareness. Objective memory performance (i.e., accuracy) did not differ based on stimulation location. In contrast, frontopolar stimulation significantly influenced several measures of memory awareness. During study, judgments of learning were more accurate such that lower ratings were given to items that were subsequently forgotten selectively following frontopolar TBS. Confidence ratings during test were also higher for correct trials following frontopolar TBS. Finally, trial-by-trial correspondence between overt performance and subjective awareness during study demonstrated a linear increase across control, dorsolateral, and frontopolar TBS locations, supporting a rostrocaudal hierarchy of prefrontal contributions to memory awareness. These findings indicate that frontopolar cortex contributes causally to memory awareness, which was improved selectively by anatomically targeted TBS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. The specialized structure of human language cortex: pyramidal cell size asymmetries within auditory and language-associated regions of the temporal lobes.

    Science.gov (United States)

    Hutsler, Jeffrey J

    2003-08-01

    Functional lateralization of language within the cerebral cortex has long driven the search for structural asymmetries that might underlie language asymmetries. Most examinations of structural asymmetry have focused upon the gross size and shape of cortical regions in and around language areas. In the last 20 years several labs have begun to document microanatomical asymmetries in the structure of language-associated cortical regions. Such microanatomic results provide useful constraints and clues to our understanding of the biological bases of language specialization in the cortex. In a previous study we documented asymmetries in the size of a specific class of pyramidal cells in the superficial cortical layers. The present work uses a nonspecific stain for cell bodies to demonstrate the presence of an asymmetry in layer III pyramidal cell sizes within auditory, secondary auditory and language-associated regions of the temporal lobes. Specifically, the left hemisphere contains a greater number of the largest pyramidal cells, those that are thought to be the origin of long-range cortico-cortical connections. These results are discussed in the context of cortical columns and how such an asymmetry might alter cortical processing. These findings, in conjunction with other asymmetries in cortical organization that have been documented within several labs, clearly demonstrate that the columnar and connective structure of auditory and language cortex in the left hemisphere is distinct from homotopic regions in the contralateral hemisphere.

  7. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  8. A Cognição Social e o Córtex Cerebral Social Cognition and the Brain Cortex

    Directory of Open Access Journals (Sweden)

    Judith Butman

    2001-01-01

    Full Text Available A cognição social é o processo que orienta condutas frente a outros indivíduos da mesma espécie. Várias estruturas cerebrais têm um papel chave para controlar as condutas sociais: o córtex pré-frontal ventromedial, a amígdala, o córtex somatosensorial direito e a ínsula. O córtex pré-frontal ventromedial está comprometido com o raciocínio social e com a tomada de decisões; a amígdala com o julgamento social de faces; o córtex somatosensorial direito, com a empatia e com a simulação; enquanto que a insula, com a resposta autonômica. Estes achados estão de acordo com a hipótese do marcador somático, um mecanismo específico por meio do qual adquirimos, representamos ou memorizamos os valores de nossas ações. Estas estruturas cerebrais atuam como mediadores entre as representações perceptuais dos estímulos sensoriais e a recuperação do conhecimento que o estímulo pode ativar. O sistema límbico é a zona limítrofe; nela, a psicologia se encontra com a neurologia. A correta sincronização destas zonas e estruturas, no adulto, é a chave para uma situação livre de patologia.Social cognition refers to the processes that subserve behavior in response to other individuals of the same species. Several brain structures play a key role in guiding social behaviors: ventromedial prefrontal cortex, amygdala, right somatosensory cortex and insula. The ventromedial prefrontal cortex is most directly involved in social reasoning and decision making; the amygdala in social judgment of faces, the right somatosensory cortex in empathy and simulation and the insula in autonomic responses. These findings are corresponding to the somatic marker hypothesis, particular mechanism by which we acquire, represent and retrieve the values of our actions. These brain structures appear to mediate between perceptual representation of social stimuli and retrieval of knowledge that such stimuli can trigger. The limbic system is the border zone

  9. [Effect of psychotropic substances and narcotic analgesics on 14C-noradrenaline uptake by rat cerebral cortex synaptosomes].

    Science.gov (United States)

    Maĭsov, N I; Tolmacheva, N S

    1980-01-01

    The effect of different groups of neurotropic substances was studied on labeled noradrenaline and gamma-aminobutyric acid (GABA) uptake by synaptosomes of the rat brain cortex. It has been shown that each group of the test compounds is characterized by specific qualitative and quantitative features of the action on the above processes. Thus, psychostimulants actively inhibit noradrenaline uptake without changing GABA uptake. On the contrary, neuroleptics exert a pronounced inhibitory effect on GABA uptake and insignificantly inhibit noradrenaline accumulation. Antidepressants are very potent while narcotic analgesic drugs are less potent inhibitors of the accumulation of both neuromediators. Morphine and nalorphine have no effect on these processes.

  10. Recovery of slow potentials in AC-coupled electrocorticography: application to spreading depolarizations in rat and human cerebral cortex

    DEFF Research Database (Denmark)

    Hartings, Jed A; Watanabe, Tomas; Dreier, Jens P

    2009-01-01

    Cortical spreading depolarizations (spreading depressions and peri-infarct depolarizations) are a pathology intrinsic to acute brain injury, generating large negative extracellular slow potential changes (SPCs) that, lasting on the order of minutes, are studied with DC-coupled recordings in animals....... The spreading SPCs of depolarization waves are observed in human cortex with AC-coupled electrocorticography (ECoG), although SPC morphology is distorted by the high-pass filter stage of the amplifiers. Here, we present a signal processing method to reverse these distortions and recover approximate full...

  11. Cerebral cavernous malformations associated with cutaneous angiokeratomas and hemangiomas.

    Science.gov (United States)

    Whitworth, Walter W; Hick, Ryan W; Nelson, Kelly C; Sidhu-Malik, Navjeet K

    2015-11-01

    We report the case of a 66-year-old man with adult-onset seizures and multiple cerebral cavernous malformations who developed numerous eruptive cutaneous angiokeratomas on the legs, scrotum, abdomen, and back as well as lobular and cavernous hemangiomas on the arms. Genetic analysis demonstrated a mutation in the KRIT1, ankyrin repeat containing gene (also known as CCM1).

  12. Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

    Science.gov (United States)

    Gardener, Samantha L; Sohrabi, Hamid R; Shen, Kai-Kai; Rainey-Smith, Stephanie R; Weinborn, Michael; Bates, Kristyn A; Shah, Tejal; Foster, Jonathan K; Lenzo, Nat; Salvado, Olivier; Laske, Christoph; Laws, Simon M; Taddei, Kevin; Verdile, Giuseppe; Martins, Ralph N

    2016-03-31

    Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific

  13. Ventrolateral and dorsomedial somatosensory association cortex damage produces distinct somesthetic syndromes in humans.

    Science.gov (United States)

    Caselli, R J

    1993-04-01

    Five somatosensory cortices have distinctive somatotopic representations, cytoarchitecture, and connectivity: primary somatosensory cortex (SI), ventrolateral association cortices (SII, SIII, and SIV), and dorsomedial association cortex (supplementary sensory area). Patients with focal lesions of ventrolateral (n = 5) and dorsomedial (n = 6) somatosensory association cortices (SACs) and hemiparetic (n = 8) and neurologically normal control patients (n = 14) underwent detailed somesthetic testing that encompassed basic, intermediate, and complex (tactile object recognition) somesthetic functions. Dorsomedial lesions acutely caused severe disruption of somesthetic processing and severe apraxia when the area of damage was extensive and involved anterior and posterior cortices. In contrast, ventrolateral lesions caused tactile agnosia. Chronically, sensorimotor function following dorsomedial damage improved considerably. Tactile agnosia following ventrolateral damage, however, was readily detectable for years following onset. Functional differences between ventrolateral and dorsomedial SACs may reflect parallel processing in dual somatosensory systems.

  14. Isolated Central Sulcus Hemorrhage: A Rare Presentation Most Frequently Associated with Cerebral Amyloid Angiopathy

    Directory of Open Access Journals (Sweden)

    Murthy R. Chamarthy

    2012-01-01

    Full Text Available Central sulcus hemorrhage is a rare imaging finding that can be related to cerebral amyloidosis in a normotensive non-traumatic elderly patient and present as an isolated finding or in association with other areas of involvement. We report a case presenting with an isolated central sulcus hemorrhage on computed tomography. Further imaging work-up excluded other potential causes of peripheral hemorrhages and established a putative diagnosis of cerebral amyloidosis.

  15. The effect of extracts of Searsia species on epileptiform activity in slices of the mouse cerebral cortex

    DEFF Research Database (Denmark)

    Pedersen, Mikael Egebjerg; Vestergaard, Henrik Tang; Stafford, Gary Ivan

    2008-01-01

    in mouse cerebral cortical slices with ED(50) of 0.62 and 1.67mg dry extract/mL, respectively. Both extracts displaced [(3)H]-GP39653 binding and significantly inhibited the NMDA-induced response during co-administration in cortical slices. CONCLUSION: In this study, the NMDA receptor antagonistic effect......ETHNOPHARMACOLOGICAL RELEVANCE: Searsia dentata and Searsia pyroides are used in traditional South African medicine to treat convulsions and epilepsy. Previous studies have demonstrated that extracts of these plants comprise compounds that bind to the flumazenil-sensitive site on the GABA......(A) receptor. However, their use as anticonvulsant medicinal plants cannot be adequately explained by these findings. AIMS: The aim of this study was to examine the possible involvement of the glutamatergic system of extracts from the plants. MATERIALS AND METHODS: The mouse cortical wedge preparation was used...

  16. Zbtb20-Induced CA1 Pyramidal Neuron Development and Area Enlargement in the Cerebral Midline Cortex of Mice

    DEFF Research Database (Denmark)

    Nielsen, Jakob V; Blom, Jonas B; Noraberg, Jens

    2010-01-01

    Expression of the transcriptional repressor Zbtb20 is confined to the hippocampal primordium of the developing dorsal midline cortex in mice. Here, we show that misexpression of Zbtb20 converts projection neurons of the subiculum and postsubiculum (dorsal presubiculum) to CA1 pyramidal neurons...... that are innervated by Schaffer collateral projections in ectopic strata oriens and radiatum. The Zbtb20-transformed neurons express Bcl11B, Satb2, and Calbindin-D28k, which are markers of adult CA1 pyramidal neurons. Downregulation of Zbtb20 expression by RNA interference impairs the normal maturation of CA1...... pyramidal neurons resulting in deficiencies in Calbindin-D28k expression and in reduced apical dendritic arborizations in stratum lacunosum moleculare. Overall, the results show that Zbtb20 is required for various aspects of CA1 pyramidal neuron development such as the postnatal extension of apical...

  17. Thermosensory Perceptual Learning Is Associated with Structural Brain Changes in Parietal-Opercular (SII) Cortex.

    Science.gov (United States)

    Mano, Hiroaki; Yoshida, Wako; Shibata, Kazuhisa; Zhang, Suyi; Koltzenburg, Martin; Kawato, Mitsuo; Seymour, Ben

    2017-09-27

    The location of a sensory cortex for temperature perception remains a topic of substantial debate. Both the parietal-opercular (SII) and posterior insula have been consistently implicated in thermosensory processing, but neither region has yet been identified as the locus of fine temperature discrimination. Using a perceptual learning paradigm in male and female humans, we show improvement in discrimination accuracy for subdegree changes in both warmth and cool detection over 5 d of repetitive training. We found that increases in discriminative accuracy were specific to the temperature (cold or warm) being trained. Using structural imaging to look for plastic changes associated with perceptual learning, we identified symmetrical increases in gray matter volume in the SII cortex. Furthermore, we observed distinct, adjacent regions for cold and warm discrimination, with cold discrimination having a more anterior locus than warm. The results suggest that thermosensory discrimination is supported by functionally and anatomically distinct temperature-specific modules in the SII cortex.SIGNIFICANCE STATEMENT We provide behavioral and neuroanatomical evidence that perceptual learning is possible within the temperature system. We show that structural plasticity localizes to parietal-opercular (SII), and not posterior insula, providing the best evidence to date resolving a longstanding debate about the location of putative "temperature cortex." Furthermore, we show that cold and warm pathways are behaviorally and anatomically dissociable, suggesting that the temperature system has distinct temperature-dependent processing modules. Copyright © 2017 Mano et al.

  18. Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

    Directory of Open Access Journals (Sweden)

    Stewart Heitmann

    2017-01-01

    Full Text Available Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40-80 Hz oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude-the hallmark of a type II excitable medium-yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields.

  19. Analysis of microRNA expression detected by microarray of the cerebral cortex after hypoxic-ischemic brain injury.

    Science.gov (United States)

    Cui, Hong; Yang, Lijun

    2013-11-01

    Small and noncoding microRNAs (miRNAs) are known as key regulators of biological processes such as cell differentiation and tumor generation. They are also the important mediators of posttranscriptional gene silencing in both pathogenic and pathologic aspects of hypoxic-ischemic brain injury. miRNA microarray has been considered to be a high-throughput and precise analysis tool for detecting miRNA expression profiling, and it does greatly facilitate the research of the biological function of miRNAs. To investigate the changes of miRNA expression in cortex of neonatal rats with hypoxic-ischemic brain injury (HIBI) and the possible roles of miRNA in the pathogenesis of HIBI, we constructed the model of rat with HIBI and the cortex tissues were obtained 14 days after the HIBI operation. The large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs of HIBI rats compared with controls. Expression of 3 miRNAs (mir-429, mir-200b, and mir-182) was determined by quantitative real-time polymerase chain reaction. The results of miRNA expression profiles indicated that 5 miRNAs were up-regulated more than twice and 29 miRNAs were down-regulated more than twice compared with the normal control group. The results of the 3 miRNAs detected by quantitative real-time polymerase chain reaction were consistent with those detected by miRNA microarray. Hypoxic-ischemic brain injury rats have significant changes in miRNA expression, which demonstrated that miRNAs may play important roles in the pathogenesis of HIBI.

  20. Fatal cerebral edema and intracranial hemorrhage associated with hypernatremic dehydration

    Energy Technology Data Exchange (ETDEWEB)

    Mocharla, R. [Department of Radiology, Slot 105, Arkansas Children`s Hospital, 800 Marshall Street, Litte Rock, AR 72202-3591 (United States); Schexnayder, S.M. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States)]|[Department of Critical Care Medicine, University of Arkansas for Medical Sciences and Arkansas Children`s Hospital, Little Rock, AR (United States); Glasier, C.M. [Department of Radiology, Slot 105, Arkansas Children`s Hospital, 800 Marshall Street, Litte Rock, AR 72202-3591 (United States)]|[Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    1997-10-01

    We report neuroimaging findings of intracranial hemorrhage and cerebral edema in an infant with obtundation and seizures, initially suspected to be secondary to non-accidental trauma but finally attributed to hypernatremic dehydration. Neuroimaging findings due to hypernatremic dehydration have not been previously described in the radiologic literature. Hypernatremia should be included in the differential diagnosis of intracranial hemorrhage in the infant without evidence of nonaccidental trauma. (orig.). With 1 fig.

  1. Cerebral Microbleeds: A Review of Clinical, Genetic and Neuroimaging Associations

    Directory of Open Access Journals (Sweden)

    Paul Andrew Yates

    2014-01-01

    Full Text Available Abstract.Cerebral microbleeds (microbleeds are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE and Susceptibility-Weighted (SWI Magnetic Resonance Imaging (MRI sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer’s disease dementia (AD and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using 11C-PiB Positron Emission Tomography (PET.The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage – particularly in the setting of anticoagulation – and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.

  2. Call-fleming syndrome (reversible cerebral artery vasoconstriction) and aneurysm associated with multiple recreational drug use.

    Science.gov (United States)

    Drazin, Doniel; Alexander, Michael J

    2013-01-01

    Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction) with an incidental aneurysm. The authors proposed their management and rationale of this complex case.

  3. Malignant Hemispheric Cerebral Infarction Associated with Idiopathic Systemic Capillary Leak Syndrome

    Directory of Open Access Journals (Sweden)

    Kei Miyata

    2013-10-01

    Full Text Available Idiopathic systemic capillary leak syndrome (ISCLS is a rare condition that is characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse general swelling, fetal hypovolemic shock, hypoalbuminemia, and hemoconcentration. Although ISCLS rarely induces cerebral infarction, we experienced a patient who deteriorated and was comatose as a result of massive cerebral infarction associated with ISCLS. In this case, severe hypotensive shock, general edema, hemiparesis, and aphasia appeared after serious antecedent gastrointestinal symptoms. Progressive life-threatening ischemic cerebral edema required decompressive hemicraniectomy. The patient experienced another episode of severe hypotension and limb edema that resulted in multiple extremity compartment syndrome. Treatment entailed forearm and calf fasciotomies. Cerebral edema in the ischemic brain progresses rapidly in patients suffering from ISCLS. Strict control of fluid volume resuscitation and aggressive diuretic therapy may be needed during the post-leak phase of fluid remobilization.

  4. Call-Fleming Syndrome (Reversible Cerebral Artery Vasoconstriction and Aneurysm Associated with Multiple Recreational Drug Use

    Directory of Open Access Journals (Sweden)

    Doniel Drazin

    2013-01-01

    Full Text Available Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction with an incidental aneurysm. The authors proposed their management and rationale of this complex case.

  5. Cerebral edema associated to scorpion sting: a two-case sting report

    Directory of Open Access Journals (Sweden)

    N. O. Romero

    2005-12-01

    Full Text Available Scorpionism is a public health problem in some places in Mexico. The clinical symptoms of envenomation by scorpion sting are by sympathetic and parasympathetic stimulation, developing systemic and local symptoms. The Central Nervous System (CNS is one of the organs that are affected. In some cases, cerebral edema develops. In this report we present two pediatric cases with the association of envenomation by scorpion sting and cerebral edema. The first case developed severe cerebral edema, which progressed to a fatal outcome; and the other case developed mild cerebral edema with a satisfactory evolution. The pathophysiology of this complication is not well known and probably is the consequence of hypoxia, secondary to respiratory failure, laryngospasm and seizures that are manifestations of envenomation by scorpion sting.

  6. The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

    Science.gov (United States)

    Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

    2016-05-01

    The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory. © 2015 Wiley Periodicals, Inc.

  7. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Directory of Open Access Journals (Sweden)

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  8. Central vestibular disorder due to ischemic injury on the parieto-insular vestibular cortex in patients with middle cerebral artery territory infarction: Observational study.

    Science.gov (United States)

    Yeo, Sang Seok; Jang, Sung Ho; Kwon, Jung Won

    2017-12-01

    Central vestibular disorder is common after middle cerebral artery (MCA) territory infarction. The MCA supplies blood to the parieto-insular vestibular cortex (PIVC), a core region of central vestibular symptoms. We report on patients that sustained injuries of the core vestibular pathway to the PIVC with central vestibular disorder following MCA territory infarction, demonstrated on diffusion tensor imaging (DTI). Nineteen patients with MCA territory infarction and 12 control subjects were recruited. To reconstruct the core vestibular pathway to the PIVC, we defined seed region of interest (ROI) as vestibular nuclei of pons and target ROI as the PIVC. Fractional anisotropy (FA), mean diffusivity, and tract volume were measured. In the affected hemisphere, FA value of the core vestibular pathway to the PIVC revealed significant difference between all patient groups and the control group (P territory infarction. Analysis of the core vestibular pathway to the PIVC using DTI would be beneficial in clinical evaluation and management of patients with MCA territory infarction. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  9. A rapid sound-action association effect in human insular cortex.

    Directory of Open Access Journals (Sweden)

    Isabella Mutschler

    Full Text Available BACKGROUND: Learning to play a musical piece is a prime example of complex sensorimotor learning in humans. Recent studies using electroencephalography (EEG and transcranial magnetic stimulation (TMS indicate that passive listening to melodies previously rehearsed by subjects on a musical instrument evokes differential brain activation as compared with unrehearsed melodies. These changes were already evident after 20-30 minutes of training. The exact brain regions involved in these differential brain responses have not yet been delineated. METHODOLOGY/PRINCIPAL FINDING: Using functional mri (fmri, we investigated subjects who passively listened to simple piano melodies from two conditions: in the 'actively learned melodies' condition subjects learned to play a piece on the piano during a short training session of a maximum of 30 minutes before the fMRI experiment, and in the 'passively learned melodies' condition subjects listened passively to and were thus familiarized with the piece. We found increased fMRI responses to actively compared with passively learned melodies in the left anterior insula, extending to the left fronto-opercular cortex. The area of significant activation overlapped the insular sensorimotor hand area as determined by our meta-analysis of previous functional imaging studies. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for differential brain responses to action-related sounds after short periods of learning in the human insular cortex. As the hand sensorimotor area of the insular cortex appears to be involved in these responses, re-activation of movement representations stored in the insular sensorimotor cortex may have contributed to the observed effect. The insular cortex may therefore play a role in the initial learning phase of action-perception associations.

  10. Neurofisiologia e plasticidade no córtex cerebral pela estimulação magnética transcraniana repetitiva Plasticity of the human cerebral cortex as revealed by transcranial magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Joaquim Brasil Neto

    2004-01-01

    Full Text Available Um velho dogma da biologia afirma que só existiria capacidade de reorganização cortical (neuroplasticidade em animais muito jovens; no adulto, tal capacidade seria pequena ou mesmo inexistente. Aqui, revisamos estudos realizados em animais e em humanos que demonstram uma capacidade de reorganização cortical nos sistemas sensoriais e motores em indivíduos adultos. Destacamos os estudos realizados com a técnica de estimulação magnética transcraniana. O córtex cerebral asulto é capaz de reorganização após lesões do sistema nervoso periférico ou central ou no contexto do aprendizado.An old biological dogma states that a potencial for cortical reorganization (neuroplasticity exists nly in young animals, being lost in adlt life. Here we review studies carried out both in animals and humans, whixh demonstrate cortical reorganization in sensory and motor systems in adult subjects. We particulary emphasiza human studies carried out with the aid of transcranial magnetic stimulation. The adult cortex is capable of reorganization after peripheral or central nervous system lesions and as a result of learning.

  11. Neuronal representation of audio-place associations in the medial prefrontal cortex of rats.

    Science.gov (United States)

    Wang, Qi; Yang, Sheng-Tao; Li, Bao-Ming

    2015-09-22

    Stimulus-place associative task requires humans or animals to associate or map different stimuli with different locations. It is know that the medial prefrontal cortex (mPFC) in rats, also termed prelimbic cortex (PrL), is important for performing stimulus-place associations. However, little is known about how mPFC neurons encode stimulus-palce associations. To address this, the present study trained rats on an audio-place associative task, whereby the animals were required to associate two different tones with entering two different arms in a Y-shaped maze. Reversible inactivation of the mPFC by local infusion of the GABAA receptor agonist muscimol severely impaired the performance of rats on the associative task, again indicating an important role of mPFC in the task performance. Single-unit recording showed that a group of mPFC neurons (40/275, 14.5 %) fired preferentially for the audio-place associations, providing the first electrophysiological evidence for the involvement of mPFC cells in representing audio-place associations.

  12. 5HT{sub 2} receptors in cerebral cortex of migraineurs studied using PET and {sup 18}F-fluorosetoperoene

    Energy Technology Data Exchange (ETDEWEB)

    Chabriat, H.; Tehindrazanarivelo, A.; Vera, P.; Samson, Y.; Pappata, S.; Boullais, N.; Bousser, M.G. [Hospital Saint Antoine, Paris (France)

    1995-04-01

    Since the brain 5HT{sub 2} might be implicated in migraine pathogenesis, the authors have used positron emission tomography and {sup 18}F-fluorosetoperone, a 5HT{sub 2} specific radioligand, to investigate in vivo the cortical 5HT{sub 2} receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura or only migraine without aura were studied between attacks. 12 unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after {sup 18}F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT{sub 2} receptors may be unaltered between attacks in migraine sufferers. 30 refs., 4 figs., 2 tabs.

  13. Temperature dependence of the sodium pump is altered in the cerebral cortex of CCK2 receptor-deficient mice.

    Science.gov (United States)

    Salum, T; Kõks, S; Kairane, C; Mahlapuu, R; Zilmer, M; Vasar, E

    2010-05-01

    Previously we have shown that the temperature dependence of the sodium pump (Na(+),K(+)-ATPase) is altered under different neuropathological conditions. In this study we compared temperature dependence of the Na(+),K(+)-ATPase in the fronto-parietal cortex of CCK(2) receptor-deficient (homo- and heterozygous) and normal (wild-type) mice. The Arrhenius plot for Na(+),K(+)-ATPase from wild-type brain is non-linear with a breakpoint at 20.3 +/- 0.4 degrees C. In case of the brain cell membrane of CCK(2) receptor-deficient mice (homo- and heterozygous) the breakpoint on Arrhenius plot was detected at 26.0 +/- 1.1 degrees C and 25.4 +/- 0.4 degrees C, respectively. The shift of the breakpoint on the Arrhenius plot established in CCK(2) receptor-deficiency as well as in case of some other pathological conditions confirms that such kind of alteration in the Na(+),K(+)-ATPase temperature dependence is likely related to the homeostatic adjustment of altered function of the sodium pump.

  14. Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois; Ferger, Boris; Beer, Ronny; Sohm, Florian; Broessner, Gregor; Hackl, Werner; Rhomberg, Paul; Lackner, Peter; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2015-12-01

    Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting. We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects. CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p < 0.001). Patients with brain edema on admission or during hospitalization (N = 20; 80 %) and patients developing DCI (N = 5; 20 %) had higher brain extracellular taurine levels compared to those without (Wald = 7.3, df = 1, p < 0.01; Wald = 10.1, df = 1, p = 0.001, respectively) even after adjusting for disease severity and CMD-probe location. There was no correlation between parenteral taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p < 0.001), lactate (r = 0.56, p < 0.02), pyruvate (r = 0.39, p < 0.01), potassium (r = 0.37, p = 0.01), and lactate-to-pyruvate ratio (r = 0.24, p = 0.02) was found. Significantly higher CMD-taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a

  15. Association rules to identify complications of cerebral infarction in patients with atrial fibrillation.

    Science.gov (United States)

    Jung, Sun-Ju; Son, Chang-Sik; Kim, Min-Soo; Kim, Dae-Joon; Park, Hyoung-Seob; Kim, Yoon-Nyun

    2013-03-01

    The purpose of this study was to find risk factors that are associated with complications of cerebral infarction in patients with atrial fibrillation (AF) and to discover useful association rules among these factors. The risk factors with respect to cerebral infarction were selected using logistic regression analysis with the Wald's forward selection approach. The rules to identify the complications of cerebral infarction were obtained by using the association rule mining (ARM) approach. We observed that 4 independent factors, namely, age, hypertension, initial electrocardiographic rhythm, and initial echocardiographic left atrial dimension (LAD), were strong predictors of cerebral infarction in patients with AF. After the application of ARM, we obtained 4 useful rules to identify complications of cerebral infarction: age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial Echo LAD (>4.06 cm); hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF). Among the induced rules, 3 factors (the initial ECG rhythm [i.e., AF], initial Echo LAD, and age) were strongly associated with each other.

  16. The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation.

    Science.gov (United States)

    Cattaneo, Zaira; Mattavelli, Giulia; Platania, Elisa; Papagno, Costanza

    2011-06-01

    Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Thicker temporal cortex associates with a developmental trajectory for psychopathic traits in adolescents.

    Directory of Open Access Journals (Sweden)

    Yaling Yang

    Full Text Available Psychopathy is a clinical condition characterized by a failure in normal social interaction and morality. Recent studies have begun to reveal brain structural abnormalities associated with psychopathic tendencies in children. However, little is known about whether variations in brain morphology are linked to the developmental trajectory of psychopathic traits over time. In this study, structural magnetic resonance imaging (sMRI data from 108 14-year-old adolescents with no history of substance abuse (54 males and 54 females were examined to detect cortical thickness variations associated with psychopathic traits and individual rates of change in psychopathic traits from ages 9 to 18. We found cortical thickness abnormalities to correlate with psychopathic traits both cross-sectionally and longitudinally. Specifically, at age 14, higher psychopathic scores were correlated with thinner cortex in the middle frontal gyrus, particularly in females, and thicker cortex in the superior temporal gyrus, middle temporal gyrus, and parahippocampal gyrus, particularly in males. Longitudinally, individual rates of change in psychopathic tendency over time were correlated with thicker cortex in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, parahippocampal gyrus, and posterior cingulate gyrus, particularly in males. Findings suggest that abnormal cortical thickness may reflect a delay in brain maturation, resulting in disturbances in frontal and temporal functioning such as impulsivity, sensation-seeking, and emotional dysregulation in adolescents. Thus, findings provide initial evidence supporting that abnormal cortical thickness may serve as a biomarker for the development of psychopathic propensity in adolescents.

  18. Thicker temporal cortex associates with a developmental trajectory for psychopathic traits in adolescents.

    Science.gov (United States)

    Yang, Yaling; Wang, Pan; Baker, Laura A; Narr, Katherine L; Joshi, Shantanu H; Hafzalla, George; Raine, Adrian; Thompson, Paul M

    2015-01-01

    Psychopathy is a clinical condition characterized by a failure in normal social interaction and morality. Recent studies have begun to reveal brain structural abnormalities associated with psychopathic tendencies in children. However, little is known about whether variations in brain morphology are linked to the developmental trajectory of psychopathic traits over time. In this study, structural magnetic resonance imaging (sMRI) data from 108 14-year-old adolescents with no history of substance abuse (54 males and 54 females) were examined to detect cortical thickness variations associated with psychopathic traits and individual rates of change in psychopathic traits from ages 9 to 18. We found cortical thickness abnormalities to correlate with psychopathic traits both cross-sectionally and longitudinally. Specifically, at age 14, higher psychopathic scores were correlated with thinner cortex in the middle frontal gyrus, particularly in females, and thicker cortex in the superior temporal gyrus, middle temporal gyrus, and parahippocampal gyrus, particularly in males. Longitudinally, individual rates of change in psychopathic tendency over time were correlated with thicker cortex in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, parahippocampal gyrus, and posterior cingulate gyrus, particularly in males. Findings suggest that abnormal cortical thickness may reflect a delay in brain maturation, resulting in disturbances in frontal and temporal functioning such as impulsivity, sensation-seeking, and emotional dysregulation in adolescents. Thus, findings provide initial evidence supporting that abnormal cortical thickness may serve as a biomarker for the development of psychopathic propensity in adolescents.

  19. A genomics approach identifies selective effects of trans-resveratrol in cerebral cortex neuron and glia gene expression.

    Directory of Open Access Journals (Sweden)

    Gemma Navarro

    Full Text Available The mode of action of trans-resveratrol, a promising lead compound for the development of neuroprotective drugs, is unknown. Data from a functional genomics study were retrieved with the aim to find differentially expressed genes that may be involved in the benefits provided by trans-resveratrol. Genes that showed a significantly different expression (p<0.05, cut-off of a two-fold change in mice fed with a control diet or a control diet containing trans-resveratrol were different in cortex, heart and skeletal muscle. In neocortex, we identified 4 up-regulated (Strap, Pkp4, Rab2a, Cpne3 and 22 down-regulated (Actn1, Arf3, Atp6v01, Atp1a3, Atp1b2, Cacng7, Crtc1, Dbn1, Dnm1, Epn1, Gfap, Hap, Mark41, Rab5b, Nrxn2, Ogt, Palm, Ptprn2, Ptprs, Syn2, Timp2, Vamp2 genes upon trans-resveratrol consumption. Network analysis of gene products provided evidence of plakophilin 4 up-regulation as a triggering factor for down-regulation of events related to synaptic vesicle transport and neurotransmitter release via underexpression of dynamin1 and Vamp2 (synaptobrevin 2 as node-gene drivers. Analysis by RT-qPCR of some of the selected genes in a glioma cell line showed that dynamin 1 mRNA was down-regulated even in acute trans-resveratrol treatments. Taken all together, these results give insight on the glial-neuronal networks involved in the neuroprotective role of trans-resveratrol.

  20. A genomics approach identifies selective effects of trans-resveratrol in cerebral cortex neuron and glia gene expression

    Science.gov (United States)

    Navarro, Gemma; Sánchez-Melgar, Alejandro; Ortiz, Raquel

    2017-01-01

    The mode of action of trans-resveratrol, a promising lead compound for the development of neuroprotective drugs, is unknown. Data from a functional genomics study were retrieved with the aim to find differentially expressed genes that may be involved in the benefits provided by trans-resveratrol. Genes that showed a significantly different expression (p<0.05, cut-off of a two-fold change) in mice fed with a control diet or a control diet containing trans-resveratrol were different in cortex, heart and skeletal muscle. In neocortex, we identified 4 up-regulated (Strap, Pkp4, Rab2a, Cpne3) and 22 down-regulated (Actn1, Arf3, Atp6v01, Atp1a3, Atp1b2, Cacng7, Crtc1, Dbn1, Dnm1, Epn1, Gfap, Hap, Mark41, Rab5b, Nrxn2, Ogt, Palm, Ptprn2, Ptprs, Syn2, Timp2, Vamp2) genes upon trans-resveratrol consumption. Network analysis of gene products provided evidence of plakophilin 4 up-regulation as a triggering factor for down-regulation of events related to synaptic vesicle transport and neurotransmitter release via underexpression of dynamin1 and Vamp2 (synaptobrevin 2) as node-gene drivers. Analysis by RT-qPCR of some of the selected genes in a glioma cell line showed that dynamin 1 mRNA was down-regulated even in acute trans-resveratrol treatments. Taken all together, these results give insight on the glial-neuronal networks involved in the neuroprotective role of trans-resveratrol. PMID:28441400

  1. Novel Rbfox2 isoforms associated with alternative exon usage in rat cortex and suprachiasmatic nucleus.

    Science.gov (United States)

    Partridge, L M M; Carter, D A

    2017-08-30

    Transcriptome diversity in adult neurons is partly mediated by RNA binding proteins (RBPs), including the RBFOX factors. RBFOX3/NeuN, a neuronal maturity marker, is strangely depleted in suprachiasmatic nucleus (SCN) neurons, and may be compensated by a change in Rbfox2 expression. In this study, we found no superficial changes in Rbfox2 expression in the SCN, but mRNA population analysis revealed a distinct SCN transcript profile that includes multiple novel Rbfox2 isoforms. Of eleven isoforms in SCN and cerebral cortex that exhibit exon variation across two protein domains, we found a 3-fold higher abundance of a novel ('-12-40') C-terminal domain (CTD)-variant in the SCN. This isoform embraces an alternative reading frame that imparts a 50% change in CTD protein sequence, and functional impairment of exon 7 exclusion activity in a RBFOX2-target, the L-type calcium channel gene, Cacna1c. We have also demonstrated functional correlates in SCN gene transcripts; inclusion of Cacna1c exon 7, and also exclusion of both NMDA receptor gene Grin1 exon 4, and Enah exon 12, all consistent with a change in SCN RBFOX activity. The demonstrated regional diversity of Rbfox2 in adult brain highlights the functional adaptability of this RBP, enabling neuronal specialization, and potentially responding to disease-related neuronal dysfunction.

  2. Cerebral blood flow associated with creative performance: a comparative study.

    Science.gov (United States)

    Chávez-Eakle, Rosa Aurora; Graff-Guerrero, Ariel; García-Reyna, Juan-Carlos; Vaugier, Víctor; Cruz-Fuentes, Carlos

    2007-11-15

    Creativity is important for social survival and individual wellbeing; science, art, philosophy and technology have been enriched and expanded by this trait. To our knowledge this is the first study probing differences in brain cerebral blood flow (CBF) between highly creative individuals (scientists and/or artists socially recognized for their contributions to their fields with creativity indexes corresponding to the 99% percentile) and average control subjects while performing a verbal task from the Torrance Tests of Creative Thinking. Additionally, we correlated CBF with creativity dimensions such as fluency, originality and flexibility. Subjects with a high creative performance showed greater CBF activity in right precentral gyrus, right culmen, left and right middle frontal gyrus, right frontal rectal gyrus, left frontal orbital gyrus, and left inferior gyrus (BA 6, 10, 11, 47, 20), and cerebellum; confirming bilateral cerebral contribution. These structures have been involved in cognition, emotion, working memory, and novelty response. The score on the three creativity dimensions--fluency, originality, and flexibility--correlated with CBF activation in right middle frontal gyrus and right rectal gyrus (Brodmann Area 6, 11). Moreover, fluency and flexibility strongly correlated with CBF in left inferior frontal gyrus and originality correlated with CBF in left superior temporal gyrus and cerebellar tonsil. These findings suggest an integration of perceptual, volitional, cognitive and emotional processes in creativity. The higher CBF found in particular brain regions of highly creative individuals during the performance of a creative task provides evidence of a specific neural network related to the creative process.

  3. Genome-wide association studies of cerebral white matter lesion burden

    NARCIS (Netherlands)

    M. Fornage (Myriam); S. Debette (Stéphanie); J.C. Bis (Joshua); R. Schmidt (Reinhold); M.A. Ikram (Arfan); C. Dufouil (Carole); S. Sigurdsson (Stefan); T. Lumley (Thomas); A.L. DeStefano (Anita); F. Fazekas (Franz); H.A. Vrooman (Henri); D.K. Shibata (Dean); P. Maillard (Pauline); A.P. Zijdenbos; A.V. Smith (Albert Vernon); H. Gudnason (Haukur); R. de Boer (Renske); M. Cushman (Mary Ann); B. Mazoyer (Bernard); G. Heiss (Gerardo); M.W. Vernooij (Meike); C. Enzinger (Christian); N.L. Glazer (Nicole); A. Beiser (Alexa); D.S. Knopman (David); M. Cavalieri (Margherita); W.J. Niessen (Wiro); T.B. Harris (Tamara); K. Petrovic (Katja); O.L. Lopez (Oscar); R. Au (Rhoda); J.C. Lambert (Jean Charles); A. Hofman (Albert); R.F. Gottesman (Rebecca); M. Garcia (Melissa); S.R. Heckbert (Susan); L.D. Atwood (Larry); D.J. Catellier (Diane); A.G. Uitterlinden (André); Q. Yang (Qiong Fang); T. Aspelund (Thor); J.R. Romero (Jose Rafael); K. Rice (Kenneth); K.D. Taylor (Kent); M.A. Nalls (Michael); J.I. Rotter (Jerome); R. Sharrett (Richey); P. Tikka-Kleemola (Päivi); P. Amouyel (Philippe); P.A. Wolf (Philip); A. van der Lugt (Aad); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); S. Seshadri (Sudha); C. Tzourio (Christophe); M.M.B. Breteler (Monique); T.H. Mosley (Thomas); W.T. Longstreth Jr; C. DeCarli (Charles); L.J. Launer (Lenore)

    2011-01-01

    textabstractObjective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased

  4. Association of lipoprotein-associated phospholipase A2 mass with asymptomatic cerebral artery stenosis.

    Science.gov (United States)

    Wang, Youxin; Zhou, Bin; Zhou, Pingan; Yao, Yan; Cui, Qinghua; Liu, Yingping; Yang, Jichun; Wu, Shouling; Zhao, Xingquan; Zhou, Yong

    2018-02-09

    Cerebral artery stenosis (CAS) is the most important causes of ischaemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays 2 diverse roles in atherosclerosis (pro-inflammatory and anti-inflammatory), and the association between Lp-PLA2 mass and cardiovascular or cerebrovascular events is inconsistent among previous studies. A cross-sectional study including 2012 North Chinese adults aged ≥40 years was performed in 2010-2011 to investigate whether Lp-PLA2 mass is associated with asymptomatic cerebral artery stenosis (ACAS). Serum Lp-PLA2 mass was determined by enzyme-linked immunosorbent assay (ELISA). All participants underwent transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS). The median serum Lp-PLA2 mass of the participants was 140.74 ng/mL (interquartile range: 131.79-158.07 ng/mL). The adjusted odds ratio (OR) when comparing the 4th quartile to the 1st quartile of Lp-PLA2 was 1.98 (95% confidence interval (CI): 1.42-2.78), 1.79 (95% CI: 1.08-2.94) and 1.87 (95% CI: 1.28-2.73) for the occurrence of ACAS, asymptomatic ECAS and asymptomatic ICAS, respectively, after controlling for vascular risk factors. These independently significant associations remained statistically significant in the male or elderly subgroups, but not in females or middle-aged participants. Lp-PLA2 mass is positively correlated with subclinical atherosclerosis determined by ACAS, ICAS and ECAS in North Chinese, particularly in male and older participants, suggesting that serum Lp-PLA2 mass might be potential biomarker for the detection of ACAS in the adults. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. Numerous cerebral hemorrhages in a patient with influenza-associated encephalitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Ye; Seong, Su Ok; Park, Noh Hyuck; Park, Chan Sup [Dept. of Radiology, Myongji Hospital, Goyang (Korea, Republic of)

    2016-02-15

    Influenza-associated encephalitis (IAE) is a complication of a common disease that is rare even during an epidemic. Awareness of magnetic resonance imaging features of IAE is important in treatment planning and prognosis estimation. Several reports have described necrotizing encephalopathy in children with influenza. However, few reports have described multifocal hemorrhages in both cerebral hemispheres in adults with concomitant infection with influenza A and B. Here, we describe a case of influenza A- and B-associated encephalitis accompanied by numerous cerebral hemorrhages.

  6. Oxidative modifications of cerebral transthyretin are associated with multiple sclerosis.

    Science.gov (United States)

    Pieragostino, Damiana; Del Boccio, Piero; Di Ioia, Maria; Pieroni, Luisa; Greco, Viviana; De Luca, Giovanna; D'Aguanno, Simona; Rossi, Claudia; Franciotta, Diego; Centonze, Diego; Sacchetta, Paolo; Di Ilio, Carmine; Lugaresi, Alessandra; Urbani, Andrea

    2013-03-01

    Transthyretin (TTR) is a homotetrameric protein of the CNS that plays a role of as the major thyroxine (T4) carrier from blood to cerebrospinal fluid (CSF). T4 physiologically helps oligodendrocyte precursor cells to turn into myelinating oligodendrocytes, enhancing remyelination after myelin sheet damage. We investigated post-translational oxidative modifications of serum and CSF TTR in multiple sclerosis subjects, highlighting high levels of S-sulfhydration and S-sulfonation of cysteine in position ten only in the cerebral TTR, which correlate with an anomalous TTR protein folding as well as with disease duration. Moreover, we found low levels of free T4 in CSF of multiple sclerosis patients, suggestive of a potential role of these modifications in T4 transport into the brain. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Reward modulation of prefrontal and visual association cortex during an incentive working memory task.

    Science.gov (United States)

    Krawczyk, Daniel C; Gazzaley, Adam; D'Esposito, Mark

    2007-04-13

    Cognitive performance differs with motivation, but little direct evidence exists regarding the neural mechanisms of the influence of reward motivation on working memory (WM). We tested the effects of motivation on the top-down control in visual WM. Encoding relevant stimuli for maintenance, while suppressing inappropriate inputs is considered a core process in cognition. Prior functional magnetic resonance imaging (fMRI) results demonstrated that stimulus-specific visual association cortex serves as a marker of activation differences for task-relevant and task-irrelevant inputs, such that enhanced activity occurs when attention is directed to relevant stimuli and suppressed activity occurs when attention is directed away from irrelevant stimuli [Gazzaley, A., Cooney, J., McEvoy, K., Knight, R.T., and D'Esposito, M. J. Cogn. Neurosci. 17, 507-517]. We used fMRI to test whether differential WM performance, indexed by lowered response times on a delayed-recognition task, was associated with amplification of enhancement and suppression effects during stimulus encoding within visual association cortex. Our results indicate that enhancement and suppression are amplified for trials with the highest reward level relative to non-rewarded trials for a scene-selective cortical region. In a face-selective region, similar modulation of enhancement for the highest reward level relative to non-rewarded trials was found. Prefrontal cortex also showed enhanced activity during high reward trials. Overall these results reveal that reward motivation can play a pivotal role in driving performance through top-down signaling in frontal regions involved in WM, as well as visual association regions selective to processing the perceptual inputs of the items to be remembered.

  8. Cocaine causes deficits in radial migration and alters the distribution of glutamate and GABA neurons in the developing rat cerebral cortex.

    Science.gov (United States)

    Lee, Chun-Ting; Chen, Jia; Worden, Lila T; Freed, William J

    2011-01-01

    Prenatal cocaine exposure induces cytoarchitectural changes in the embryonic neocortex; however, the biological mechanisms and type of cortical neurons involved in these changes are not known. Previously, we found that neural progenitor proliferation in the neocortical ventricular zone (VZ) is inhibited by cocaine; here, we examine the changes in cortical neurogenesis and migration of glutamate and GABA neurons induced by prenatal cocaine exposure. Pregnant rats received 20 mg/kg of cocaine intraperitoneally twice at an interval of 12 h during three periods of neocortical neurogenesis. Neocortical area and distribution of developing neurons were examined by counting Tuj1+, glutamate+, or GABA+ cells in different areas of the cerebral cortex. Cocaine decreased neocortical area by reducing the size of the Tuj1+ layer, but only when administered during early periods of neocortical neurogenesis. The number of glutamatergic neurons was increased in the VZ but was decreased in the outer cortical laminae. Although the number of GABA+ neurons in the VZ of both the neocortex and ganglionic eminences was unchanged, GABA+ cells decreased in all other neocortical laminae. Tangential migration of GABA+ cells was also disrupted by cocaine. These findings suggest that in utero cocaine exposure disturbs radial migration of neocortical neurons, possibly because of decreased radial glia guiding support through enhanced differentiation of neocortical VZ progenitors. Cocaine interrupts radial migration of both glutamatergic and GABAergic neurons within the neocortex, in addition to the tangential migration of GABAergic neurons from the subcortical telecephalon. This may result in abnormal neocortical cytoarchitecture and concomitant adverse functional effects. Copyright © 2010 Wiley-Liss, Inc.

  9. Beta-amyloid (1-42)-induced learning and memory deficits in mice: involvement of oxidative burdens in the hippocampus and cerebral cortex.

    Science.gov (United States)

    Jhoo, Jin Hyeong; Kim, Hyoung-Chun; Nabeshima, Toshitaka; Yamada, Kiyofumi; Shin, Eun-Joo; Jhoo, Wang-Kee; Kim, Wookyung; Kang, Kee-Seok; Jo, Sangmee Ahn; Woo, Jong Inn

    2004-12-06

    We have demonstrated that oxidative stress is involved, at least in part, in beta-amyloid protein (Abeta)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Abeta remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Abeta (1-42) in mice. Abeta (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Abeta (40-1)-treated mice. Treatment with antioxidant alpha-tocopherol significantly prevented memory impairment induced by Abeta (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Abeta (1-42)-treated animals, as compared with Abeta (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Abeta (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Abeta (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2h after Abeta (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Abeta (1-42), but the antioxidant alpha-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Abeta (1-42)-induced learning and memory deficits in mice.

  10. Laminar and cytoarchitectonic features of the cerebral cortex in the Risso's dolphin (Grampus griseus), striped dolphin (Stenella coeruleoalba), and bottlenose dolphin (Tursiops truncatus).

    Science.gov (United States)

    Furutani, Rui

    2008-09-01

    The present investigation carried out Nissl, Klüver-Barrera, and Golgi studies of the cerebral cortex in three distinct genera of oceanic dolphins (Risso's dolphin, striped dolphin and bottlenose dolphin) to identify and classify cortical laminar and cytoarchitectonic structures in four distinct functional areas, including primary motor (M1), primary sensory (S1), primary visual (V1), and primary auditory (A1) cortices. The laminar and cytoarchitectonic organization of each of these cortical areas was similar among the three dolphin species. M1 was visualized as five-layer structure that included the molecular layer (layer I), external granular layer (layer II), external pyramidal layer (layer III), internal pyramidal layer (layer V), and fusiform layer (layer VI). The internal granular layer was absent. The cetacean sensory-related cortical areas S1, V1, and A1 were also found to have a five-layer organization comprising layers I, II, III, V and VI. In particular, A1 was characterized by the broadest layer I, layer II and developed band of pyramidal neurons in layers III (sublayers IIIa, IIIb and IIIc) and V. The patch organization consisting of the layer IIIb-pyramidal neurons was detected in the S1 and V1, but not in A1. The laminar patterns of V1 and S1 were similar, but the cytoarchitectonic structures of the two areas were different. V1 was characterized by a broader layer II than that of S1, and also contained the specialized pyramidal and multipolar stellate neurons in layers III and V.

  11. A rare association of cerebral dural arteriovenous fistula with venous aneurysm and contralateral flow-related middle cerebral artery aneurysm.

    Science.gov (United States)

    Onu, David O; Hunn, Andrew W; Harle, Robin A

    2013-09-19

    The association of cerebral dural arteriovenous fistula (DAVF) and ipsilateral flow related aneurysm has infrequently been reported. We describe a male patient who presented with an acute haemorrhagic stroke and was found to have a large right fronto-parietal intra-parenchymal haemorrhage from the ruptured Borden type II DAVF in addition to a large venous aneurysm and a flow related intraosseous aneurysm of the contralateral middle meningeal artery (MMA) all clearly delineated by CT and DSA. He underwent emergency stereotactic evacuation of the intraparenchymal haemorrhage and successful surgical treatment of all the vascular lesions at the same time with residual neurological deficit. To our knowledge, this is the first such reported case. We discuss the challenging surgical treatment, emphasising the role of CT/DSA in management, and provide a literature review.

  12. Reduced pyramidal cell somal volume in auditory association cortex of subjects with schizophrenia.

    Science.gov (United States)

    Sweet, Robert A; Pierri, Joseph N; Auh, Sungyoung; Sampson, Allan R; Lewis, David A

    2003-03-01

    Subjects with schizophrenia have decreased gray matter volume of auditory association cortex in structural imaging studies, and exhibit deficits in auditory sensory memory processes subserved by this region. In dorsal prefrontal cortex (dPFC), similar in vivo observations of reduced regional volume and working memory deficits in subjects with schizophrenia have been related to reduced somal volume of deep layer 3 pyramidal cells. We hypothesized that deep layer 3 pyramidal cell somal volume would also be reduced in auditory association cortex (BA42) in schizophrenia. We used the nucleator to estimate the somal volume of pyramidal neurons in deep layer 3 of BA42 in 18 subjects with schizophrenia, each of whom was matched to one normal comparison subject for gender, age, and post-mortem interval. For all subject pairs, somal volume of pyramidal neurons in deep layer 3 of dPFC (BA9) had previously been determined. In BA42, somal volume was reduced by 13.1% in schizophrenic subjects (p=0.03). Reductions in somal volume were not associated with the history of antipsychotic use, alcohol dependence, schizoaffective disorder, or death by suicide. The percent change in somal volume within-subject pairs was highly correlated between BA42 and BA9 (r=0.67, p=0.002). Deep layer 3 pyramidal cell somal volume is reduced in BA42 of subjects with schizophrenia. This reduction may contribute to impairment in auditory function. The correlated reductions of somal volume in BA42 and BA9 suggest that a common factor may affect deep layer 3 pyramidal cells in both regions.

  13. Cytomegalovirus and Epstein-Barr virus may be associated with some cases of cerebral palsy.

    Science.gov (United States)

    McMichael, Gai; MacLennan, Alastair; Gibson, Catherine; Alvino, Emily; Goldwater, Paul; Haan, Eric; Dekker, Gustaaf

    2012-10-01

    Intrauterine infection is a risk factor for cerebral palsy. Previous work reported a high frequency of viral DNA in newborn screening cards from cerebral palsy cases and controls possibly due to contamination. Retrospective case-control study using improved methodologies to minimize contamination during PCR-based detection of viral DNA sequences. Newborn screening cards of 339 Caucasian children with cerebral palsy and 594 controls were examined. Viruses tested were herpes simplex viruses 1 and 2 (HSV1 and 2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes viruses 6, 7 and 8 (HHV6, HHV7 and HHV8), and parvovirus B19. Genotyping was performed on DNA extracted from dried blood spots. CMV and EBV were detected in 5 (1.5%) and 3 (0.9%) of 339 cases, respectively, but not in controls (p = 0.047 and 0.006). Frequencies of detection of the other viruses examined were similar for cases and controls. DNA from at least one of the nine viruses tested was found in 4.4% of cases and 3.1% of controls [OR 1.4 95% CI (0.71-2.76)]. Evidence of congenital viral infection was uncommon in cases of cerebral palsy and controls. However, CMV and EBV were significantly associated with cerebral palsy.

  14. A Case Associated with Comorbidities Among Cerebral Infarction, Idiopathic Thrombocytopenic Purpura, and Triple X Syndrome

    Directory of Open Access Journals (Sweden)

    Hanjun Kim

    2014-06-01

    Full Text Available A 46-year-old female presented to the emergency room due to the chief complaint of left-sided weakness. By imaging study, she was diagnosed with cerebral infarction. Thrombolytic and antiplatelet agents were not considered due to the “golden hour” for treatment having passed and a low platelet count. The peripheral blood smear, bone marrow biopsy, and aspirate findings were consistent with immune thrombocytopenic purpura. The chromosome analysis revealed the 47,XXX karyotype. To the best of our knowledge, this is the first case report associated with the comorbidities of cerebral infarction, idiopathic thrombocytopenic purpura, and triple X syndrome.

  15. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2013-01-01

    Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood amm...

  16. Associations between Handedness and Cerebral Lateralisation for Language: A Comparison of Three Measures in Children

    NARCIS (Netherlands)

    Groen, M.A.; Whitehouse, A.J.O.; Badcock, N.A.; Bishop, D.V.M.

    2013-01-01

    It has been known for many years that hand preference is associated with cerebral lateralisation for language, but the relationship is weak and indirect. It has been suggested that quantitative measures of differential hand skill or reaching preference may provide more valid measures than

  17. Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia

    DEFF Research Database (Denmark)

    Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M

    2018-01-01

    Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention tr...

  18. Aerobic fitness is associated with greater hippocampal cerebral blood flow in children

    Directory of Open Access Journals (Sweden)

    Laura Chaddock-Heyman

    2016-08-01

    Full Text Available The present study is the first to investigate whether cerebral blood flow in the hippocampus relates to aerobic fitness in children. In particular, we used arterial spin labeling (ASL perfusion MRI to provide a quantitative measure of blood flow in the hippocampus in 73 7- to 9-year-old preadolescent children. Indeed, aerobic fitness was found to relate to greater perfusion in the hippocampus, independent of age, sex, and hippocampal volume. Such results suggest improved microcirculation and cerebral vasculature in preadolescent children with higher levels of aerobic fitness. Further, aerobic fitness may influence how the brain regulates its metabolic demands via blood flow in a region of the brain important for learning and memory. To add specificity to the relationship of fitness to the hippocampus, we demonstrate no significant association between aerobic fitness and cerebral blood flow in the brainstem. Our results reinforce the importance of aerobic fitness during a critical period of child development.

  19. Association Between Maternal Body Mass Index in Early Pregnancy and Incidence of Cerebral Palsy.

    Science.gov (United States)

    Villamor, Eduardo; Tedroff, Kristina; Peterson, Mark; Johansson, Stefan; Neovius, Martin; Petersson, Gunnar; Cnattingius, Sven

    2017-03-07

    Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms. To study the associations between early pregnancy body mass index (BMI) and rates of cerebral palsy by gestational age and to identify potential mediators of these associations. Population-based retrospective cohort study of women with singleton children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012. Early pregnancy BMI. Incidence rates of cerebral palsy and hazard ratios (HRs) with 95% CIs, adjusted for maternal age, country of origin, education level, cohabitation with a partner, height, smoking during pregnancy, and year of delivery. Of 1 423 929 children included (mean gestational age, 39.8 weeks [SD, 1.8]; 51.4% male), 3029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up (risk, 2.13 per 1000 live births; rate, 2.63/10 000 child-years). The percentages of mothers in BMI categories were 2.4% at BMI less than 18.5 (underweight), 61.8% at BMI of 18.5 to 24.9 (normal weight), 24.8% at BMI of 25 to 29.9 (overweight), 7.8% at BMI of 30 to 34.9 (obesity grade 1), 2.4% at BMI of 35 to 39.9 (obesity grade 2), and 0.8% at BMI 40 or greater (obesity grade 3). The number of cerebral palsy cases in each BMI category was 64, 1487, 728, 239, 88, and 38; and the rates per 10 000 child-years were 2.58, 2.35, 2.92, 3.15, 4.00, and 5.19, respectively. Compared with children of normal-weight mothers, adjusted HR of cerebral palsy were 1.22 (95% CI, 1.11-1.33) for overweight, 1.28 (95% CI, 1.11-1.47) for obesity grade 1, 1.54 (95% CI, 1.24, 1.93) for obesity grade 2, and 2.02 (95% CI, 1

  20. Cerebral blood flow reduction associated with orientation for time in amnesic mild cognitive impairment and Alzheimer disease patients.

    Science.gov (United States)

    Yamashita, Ken-Ichiro; Taniwaki, Yoshihide; Utsunomiya, Hidetsuna; Taniwaki, Takayuki

    2014-01-01

    Impairment of orientation for time (OT) is a characteristic symptom of Alzheimer disease (AD). However, the brain regions underlying OT remain to be elucidated. Using single photon emission computed tomography (SPECT), we examined the brain regions exhibiting hypoperfusion that were associated with OT. We compared regional cerebral blood flow (rCBF) differences between AD and amnesic mild cognitive impairment (aMCI) or normal subjects using 3-dimensional stereotactic surface projection (3D-SSP) analysis. AD patients were divided into OT good and poor groups according to their mean OT scores, and rCBF then compared between the groups to elucidate OT-specific brain areas. 3D-SSP analysis showed reduced rCBF in the left superior parietal lobule (SPL) and bilateral inferior parietal lobule (IPL) in AD patients. In the poor OT group, 3D-SSP analysis revealed hypoperfusion in the bilateral SPL, IPL, posterior cingulated cortex (PCC), and precuneus. Among these areas, region of interest analysis revealed a significant higher number of hypoperfused pixels in the left PCC in the OT poor AD group. Our SPECT study suggested that hypoperfusion in the left SPL and bilateral IPL was AD specific, and reduced rCBF in the left PCC was specifically associated with OT. Copyright © 2014 by the American Society of Neuroimaging.

  1. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

    Science.gov (United States)

    Taylor, Matthew K; Sullivan, Debra K; Swerdlow, Russell H; Vidoni, Eric D; Morris, Jill K; Mahnken, Jonathan D; Burns, Jeffrey M

    2017-12-01

    Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging.Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults.Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing.Results: Amyloid was elevated in 26% (n = 33) of participants. HGLDiet pattern adherence (P = 0.01), sugar intake (P = 0.03), and carbohydrate intake (P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level (P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education.Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer disease

  2. The Emerging Neurobiology of Attention Deficit Hyperactivity Disorder: The Key Role of the Prefrontal Association Cortex

    Science.gov (United States)

    Arnsten, Amy F.T.

    2009-01-01

    Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and locomotor hyperactivity. Recent advances in neurobiology, imaging, and genetics have led to a greater understanding of the etiology and treatment of ADHD. Studies have found that ADHD is associated with weaker function and structure of prefrontal cortex (PFC) circuits, especially in the right hemisphere. The prefrontal association cortex plays a crucial role in regulating attention, behavior, and emotion, with the right hemisphere specialized for behavioral inhibition. The PFC is highly dependent on the correct neurochemical environment for proper function: noradrenergic stimulation of postsynaptic alpha-2A adrenoceptors and dopaminergic stimulation of D1 receptors is necessary for optimal prefrontal function. ADHD is associated with genetic changes that weaken catecholamine signaling and, in some patients, with slowed PFC maturation. Effective pharmacologic treatments for ADHD all enhance catecholamine signaling in the PFC and strengthen its regulation of attention and behavior. Recent animal studies show that therapeutic doses of stimulant medications preferentially increase norepinephrine and, to a lesser extent, dopamine, in the PFC. These doses reduce locomotor activity and improve PFC regulation of attention and behavior through enhanced catecholamine stimulation of alpha-2A and D1 receptors. These findings in animals are consistent with improved PFC function in normal human subjects and, more prominently, in patients with ADHD. Thus, a highly cohesive story is emerging regarding the etiology and treatment of ADHD. PMID:20596295

  3. The neurobiology of glucocerebrosidase-associated parkinsonism: a positron emission tomography study of dopamine synthesis and regional cerebral blood flow

    Science.gov (United States)

    Goker-Alpan, Ozlem; Masdeu, Joseph C.; Kohn, Philip D.; Ianni, Angela; Lopez, Grisel; Groden, Catherine; Chapman, Molly C.; Cropp, Brett; Eisenberg, Daniel P.; Maniwang, Emerson D.; Davis, Joie; Wiggs, Edythe; Berman, Karen F.

    2012-01-01

    Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls. Patients with GBA mutations generally have an earlier onset of Parkinson disease and more cognitive impairment than those without GBA mutations. We investigated whether GBA mutations alter the neurobiology of Parkinson disease, studying brain dopamine synthesis and resting regional cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine synthesis with 18F-fluorodopa positron emission tomography, and resting regional cerebral blood flow with H215O positron emission tomography in the wakeful, resting state in four study groups: (i) patients with Parkinson disease and Gaucher disease (n = 7, average age = 56.6 ± 9.2 years); (ii) patients with Parkinson disease without GBA mutations (n = 11, 62.1 ± 7.1 years); (iii) patients with Gaucher disease without parkinsonism, but with a family history of Parkinson disease (n = 14, 52.6 ± 12.4 years); and (iv) healthy GBA-mutation carriers with a family history of Parkinson disease (n = 7, 50.1 ± 18 years). We compared each study group with a matched control group. Data were analysed with region of interest and voxel-based methods. Disease duration and Parkinson disease functional and staging scores were similar in the two groups with parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction in the caudate (20 and 18% loss). However, the group with both Parkinson and Gaucher diseases showed decreased resting regional cerebral blood flow in the lateral parieto-occipital association cortex and precuneus bilaterally. Furthermore, two subjects with Gaucher disease without parkinsonian manifestations showed diminished striatal dopamine. In conclusion, the

  4. Organization of Estrogen-Associated Circuits in the Mouse Primary Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Liisa A. Tremere

    2011-01-01

    Full Text Available Sex steroid hormones influence the perceptual processing of sensory signals in vertebrates. In particular, decades of research have shown that circulating levels of estrogen correlate with hearing function. The mechanisms and sites of action supporting this sensory-neuroendocrine modulation, however, remain unknown. Here we combined a molecular cloning strategy, fluorescence in-situ hybridization and unbiased quantification methods to show that estrogen-producing and -sensitive neurons heavily populate the adult mouse primary auditory cortex (AI. We also show that auditory experience in freely-behaving animals engages estrogen-producing and -sensitive neurons in AI. These estrogen-associated networks are greatly stable, and do not quantitatively change as a result of acute episodes of sensory experience. We further demonstrate the neurochemical identity of estrogen-producing and estrogen-sensitive neurons in AI and show that these cell populations are phenotypically distinct. Our findings provide the first direct demonstration that estrogen-associated circuits are highly prevalent and engaged by sensory experience in the mouse auditory cortex, and suggest that previous correlations between estrogen levels and hearing function may be related to brain-generated hormone production. Finally, our findings suggest that estrogenic modulation may be a central component of the operational framework of central auditory networks.

  5. Habitual 'sleep credit' is associated with greater grey matter volume of the medial prefrontal cortex, higher emotional intelligence and better mental health.

    Science.gov (United States)

    Weber, Mareen; Webb, Christian A; Deldonno, Sophie R; Kipman, Maia; Schwab, Zachary J; Weiner, Melissa R; Killgore, William D S

    2013-10-01

    In modern society, people often fail to obtain the amount of sleep that experts recommend for good health and performance. Insufficient sleep can lead to degraded cognitive performance and alterations in emotional functioning. However, most people also acknowledge that on a regular basis they obtain more sleep than they subjectively perceive they need at a minimum to stave off performance decrements, a construct we describe as subjective 'sleep credit'. Few people would contest the notion that getting more sleep is better, but data on both behavioural and neuroanatomical correlates of 'sleep credit' are surprisingly limited. We conducted a voxel-based morphometric study to assess cerebral grey matter correlates of habitually sleeping more than one's subjective requirements. We further tested whether these structural correlates are associated with perceived emotional intelligence and indices of psychopathology while controlling for age, gender, and total intracranial volume. In a sample of 55 healthy adults aged 18-45 years (28 males, 27 females), whole-brain multiple regression showed that habitual subjective 'sleep credit' was correlated positively with grey matter volume within regions of the left medial prefrontal cortex and right orbitofrontal gyrus. Volumes were extracted and regressed against self-report emotion and psychopathology indices. Only grey matter volume of the medial prefrontal cortex cluster correlated with greater emotional intelligence and lower scores on several indices of psychopathology. Findings converge with previous evidence of the role of the medial prefrontal cortex in the relationship between sleep and emotional functioning, and suggest that behaviour and brain structure vary with habitual 'sleep credit'. © 2013 European Sleep Research Society.

  6. Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia.

    Science.gov (United States)

    Vallortigara, Julie; Rangarajan, Sindhoo; Whitfield, David; Alghamdi, Amani; Howlett, David; Hortobágyi, Tibor; Johnson, Mary; Attems, Johannes; Ballard, Clive; Thomas, Alan; O'Brien, John; Aarsland, Dag; Francis, Paul

    2014-01-01

    Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer's disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques - tangles) and for α-synuclein (Lewy bodies). Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex. On one hand, levels of Dynamin1 were significantly reduced, and correlated with a higher rate of cognitive decline observed in cases from three dementia groups. On the other hand, the fraction of phospho-CaMKII was decreased, and correlated with a high score of plaques and tangles in BA9. Interestingly, the correlation between the rate of cognitive decline and the level of Dynamin1 remained when the analysis was restricted to the PDD and DLB cases, highlighting an association of Dynamin1 with cognitive decline in people with Lewy Body dementia.

  7. Distribution of high-voltage-activated calcium channels in cultured gamma-aminobutyric acidergic neurons from mouse cerebral cortex.

    Science.gov (United States)

    Timmermann, Daniel B; Westenbroek, Ruth E; Schousboe, Arne; Catterall, William A

    2002-01-01

    The localization of voltage-gated calcium channel (VGCC) alpha(1) subunits in cultured GABAergic mouse cortical neurons was examined by immunocytochemical methods. Ca(v)1.2 and Ca(v)1.3 subunits of L-type VGCCs were found in cell bodies and dendrites of GABA-immunopositive neurons. Likewise, the Ca(v)2.3 subunit of R-type VGCCs was expressed in a somatodendritic pattern. Ca(v)2.2 subunits of N-type channels were found exclusively in small varicosities that were identified as presynaptic nerve terminals based on their expression of synaptic marker proteins. Two splice variants of the Ca(v)2.1 subunit of P/Q-type VGCCs showed widely differing expression patterns. The rbA isoform displayed a purely somatodendritic staining pattern, whereas the BI isoform was confined to axon-like fibers and nerve terminals. The nerve terminals of these cultured GABAergic neurons express Ca(v)2.2 either alone or in combination with Ca(v)2.1 (BI isoform) but never express Ca(v)2.1 alone. The functional association between VGCCs and the neurotransmitter release machinery was probed using the FM1-43 dye-labeling technique. N-type VGCCs were found to be tightly coupled to exocytosis in these cultured cortical neurons, and P-type VGCCs were also important in a fraction of the cells. The predominant role of N-type VGCCs in neurotransmitter release and the specific localization of the BI isoform of Ca(v)2.1 in the nerve terminals of these neurons distinguish them from previously studied central neurons. The complementary localization patterns observed for two different isoforms of the Ca(v)2.1 subunits provide direct evidence for alternative splicing as a means of generating functional diversity among neuronal calcium channels. Copyright 2002 Wiley-Liss, Inc.

  8. Depressive Symptom Dimensions and Their Association with Hippocampal and Entorhinal Cortex Volumes in Community Dwelling Older Adults

    Directory of Open Access Journals (Sweden)

    Deirdre M. O’Shea

    2018-02-01

    Full Text Available Objective: Research has shown that depression is a risk factor for Alzheimer’s disease (AD and subsequent cognitive decline. This is compounded by evidence showing an association between depression and reduced hippocampal volumes; a primary structure implicated in the pathogenesis of the disease. Less is known about the relationship between depression and other AD vulnerable regions such as the entorhinal cortex. Given the heterogeneity of depressive symptom presentation, we examined whether symptom dimensions were associated with hippocampal and entorhinal cortex volumes in community dwelling older adults.Methods: Eighty-one community dwelling adults completed the Beck Depression Inventory – second edition and underwent structural neuroimaging. Measures of hippocampal and entorhinal cortex volumes were obtained using FreeSurfer software. Linear regression models included regions of interest as dependent variables, with depressive symptom dimensions, as independent variables, controlling for total intracranial volumes, age, education, and gender.Results: Somatic symptoms were negatively associated with total, right, and left hippocampal volumes. Affective symptoms were negatively associated with total entorhinal cortex volumes, with a marginal main effect on left entorhinal cortex volumes.Conclusion: Our findings provide support for examining depressive symptoms and their association with AD vulnerable regions along subdimensions of affective, cognitive, and somatic symptoms to better understand profiles of symptoms most associated with these regions. Conceptualizing depressive symptoms in this way may also better inform treatment approaches in terms of targeting types of symptoms that may be more closely linked to poorer brain and cognitive health outcomes.

  9. Normobaric hyperoxia is associated with increased cerebral excitotoxicity after severe traumatic brain injury.

    Science.gov (United States)

    Quintard, Hervé; Patet, Camille; Suys, Tamarah; Marques-Vidal, Pedro; Oddo, Mauro

    2015-04-01

    Normobaric oxygen therapy is frequently applied in neurocritical care, however, whether supplemental FiO2 has beneficial cerebral effects is still controversial. We examined in patients with severe traumatic brain injury (TBI) the effect of incremental FiO2 on cerebral excitotoxicity, quantified by cerebral microdialysis (CMD) glutamate. This was a retrospective analysis of a database of severe TBI patients monitored with CMD and brain tissue oxygen (PbtO2). The relationship of FiO2--categorized into four separate ranges (80 %)--with CMD glutamate was examined using ANOVA with Tukey's post hoc test. A total of 1,130 CMD samples from 36 patients--monitored for a median of 4 days--were examined. After adjusting for brain (PbtO2, intracranial pressure, cerebral perfusion pressure, lactate/pyruvate ratio, Marshall CT score) and systemic (PaCO2, PaO2, hemoglobin, APACHE score) covariates, high FiO2 was associated with a progressive increase in CMD glutamate [8.8 (95 % confidence interval 7.4-10.2) µmol/L at FiO2 80 %; multivariate-adjusted p CMD glutamate was lower for samples with normal versus low PbtO2 40 % vs. FiO2 > 60 %). Hyperoxia (PaO2 > 150 mmHg) was also associated with increased CMD glutamate (adjusted p oxygen may aggravate secondary brain damage after severe TBI.

  10. Cerebral Salt-Wasting Associated with the Guillain-Barre Syndrome

    Science.gov (United States)

    1965-07-01

    symptoms of upper- ’able from the Guillain - Barr syndrome and of respiratory-tract infection or history of other ante- [u! ,,• " ,•cedent illness...Medical Association Cerebral Salt-Wasting VE Associated With the Guillain - Barre Syndrome LT CDR WILLIAM C. COOPER, MC, USN, LT CDR IRVING J. GREEN...and low backache. I • with the salt-wasting syndrome .14 The follow- These symptoms progressed, the left leg became : . ing is a report of the

  11. The short-term toxicity of ethanol to neurons in rat cerebral cortex tested by topical application in vivo, and a note on a problem in estimating ethanol concentrations in tissue.

    Science.gov (United States)

    Phillips, S C; Cragg, B G; Singh, S C

    1981-03-01

    In rats anesthetized with ethanol 4.0 g/kg i.p. the dura overlying the parietal cortex was exposed and superfused with 100% ethanol for 1 h. After 6 days survival the underlying cortex was stained with a silver method that is selective for degenerating axons and their terminals. No degeneration was found in the superfused cortex, although heat-lesioned tissue stained concurrently showed axonal degeneration and so validated the technique. Electron microscopy after 3-20 days survival did not show any degeneration, and synapses of normal appearance were present immediately beneath the cortical surface. In other rats the ethanol concentration in the superfused tissue was assayed in 0.4 mm thick discs sectioned with a vibratome from a 4-mm diameter core cut with a trocar from the cortex immediately after 1 h of superfusion. The ethanol was eluted in 2% TCA, and an aliquot assayed enzymatically. A second elution of the tissue disc contributed a further 5% of the ethanol content indicating a partition coefficient for ethanol between wet brain tissue and 2% TCA of about 10. The total concentration of ethanol in the superficial cortex was found to be about 0.82 M or 3.8%. This estimation was confirmed by superfusion with 14C-labelled ethanol and scintillation counting. Thus neurons in the cerebral cortex did not degenerate after exposure for 1 h to a concentration of ethanol that was 3 times greater than the concentration that causes death in a rat by paralysis of the respiratory centre (1.2%).

  12. A novel CCM1 mutation associated with multiple cerebral and vertebral cavernous malformations.

    Science.gov (United States)

    Lanfranconi, Silvia; Ronchi, Dario; Ahmed, Naghia; Civelli, Vittorio; Basilico, Paola; Bresolin, Nereo; Comi, Giacomo Pietro; Corti, Stefania

    2014-08-03

    Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part of the central nervous system. This presentation has been associated with heterozygous mutations in CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10. We aimed to investigate the genetic defect underlying multiple cerebral and vertebral cavernous malformations in a multigenerational Italian family. The proband is a 49-year-old man who underwent cerebral MRI in his thirties for persistent haeadache and tingling in his left arm and leg and was diagnosed with multiple supratentorial cavernous angiomas. A right frontal angioma with radiological evidence of a recent bleeding was surgically removed when he was 39 years old and he was thereafter asymptomatic. Magnetic resonance imaging revealed multiple cerebral cavernous malformations in seven members of his familily. Four subjects were asymptomatic. Other family mambers displayed heterogeneous clinical features including seizures and recurrent brain haemorrhages. Sequence analysis in the proband disclosed a novel heterozygous nucleotide substitution (c.263-10A > G) in intron 5 of CCM1. This variant is predicted to create an abnormal acceptor splice site and segregated in affected relatives available for molecular screening. The analysis of CCM1 transcript in proband's lymphocytes confirmed the partial retention of intron 3 resulting in a premature termination codon. Our findings demonstrate that c.263-10A > G mutation is associated with cerebral cavernous malformations. A better knowledge of the disease-associated phenotype may lead to an early diagnosis and to an appropriate clinical surveillance in affected patients.

  13. Altered Coupling between Motion-Related Activation and Resting-State Brain Activity in the Ipsilesional Sensorimotor Cortex after Cerebral Stroke

    Directory of Open Access Journals (Sweden)

    Jianping Hu

    2017-07-01

    Full Text Available Functional connectivity maps using resting-state functional magnetic resonance imaging (rs-fMRI can closely resemble task fMRI activation patterns, suggesting that resting-state brain activity may predict task-evoked activation or behavioral performance. However, this conclusion was mostly drawn upon a healthy population. It remains unclear whether the predictive ability of resting-state brain activity for task-evoked activation would change under different pathological conditions. This study investigated dynamic changes of coupling between patterns of resting-state functional connectivity (RSFC and motion-related activation in different stages of cerebral stroke. Twenty stroke patients with hand motor function impairment were involved. rs-fMRI and hand motion-related fMRI data were acquired in the acute, subacute, and early chronic stages of cerebral stroke on a 3-T magnetic resonance (MR scanner. Sixteen healthy participants were enrolled as controls. For each subject, an activation map of the affected hand was first created using general linear model analysis on task fMRI data, and then an RSFC map was determined by seeding at the peak region of hand motion activation during the intact hand task. We then measured the extent of coupling between the RSFC maps and motion-related activation maps. Dynamic changes of the coupling between the two fMRI maps were estimated using one-way repeated measures analysis of variance across the three stages. Moreover, imaging parameters were correlated with motor performances. Data analysis showed that there were different coupling patterns between motion-related activation and RSFC maps associating with the affected motor regions during the acute, subacute, and early chronic stages of stroke. Coupling strengths increased as the recovery from stroke progressed. Coupling strengths were correlated with hand motion performance in the acute stage, while coupling recovery was negatively correlated with the recovery

  14. Inhalation of air polluted with gasoline vapours alters the levels of amino acid neurotransmitters in the cerebral cortex, hippocampus, and hypothalamus of the rat.

    Science.gov (United States)

    Kinawy, Amal A; Ezzat, Ahmed R; Al-Suwaigh, Badryah R

    2014-08-01

    This study was designed to investigate the impact of exposure to the vapours of two kinds of gasoline, a widely used fuel for the internal combustion engines on the levels of the amino acid neurotransmitters of the rat brain. Recent studies provide strong evidence for a causative role for traffic-related air pollution on morbidity outcomes as well as premature death (Health Effects Institute, 2009; Levy et al., 2010; von Stackelberg et al., 2013). Exposure to the vapours of gasoline or its constituents may be accidental, occupational by workers at fuel stations and factories, or through abuse as a mean of mood alteration (Fortenberry, 1985; Mc Garvey et al., 1999). Two kinds of gasoline that are common in Egypt have been used in this study. The first contains octane enhancers in the form of lead derivatives (leaded gasoline; G1) and the other contains methyl-tertiary butyl ether (MTBE) as the octane enhancer (unleaded gasoline; G2). The levels of the major excitatory (aspartic acid and glutamic acid) and the inhibitory (GABA and glycine) amino acid neurotransmitters were determined in the cerebral cortex, hippocampus, and hypothalamus. The current study revealed that the acute inhalation of air polluted with the two types of gasoline vapours (1/2 LC50 for 30 min) induced elevation in the levels of aspartic and glutamic acids along with a decrease in glycine and GABA in most studied brain areas. Chronic inhalation of both types of gasoline (a single daily 30-min session of 1/5 LC50 for 60 days) caused a significant increase in the aspartic and glutamic acid concentrations of the hippocampus without affecting the levels of GABA or glycine. Acute and chronic inhalation of either one of G1 and G2 vapours induced a disturbance and fluctuation in the levels of the free amino acids that act as excitatory and inhibitory neurotransmitters in the brain areas under investigation. These neurotransmitters are fundamental for the communicative functioning of the neurons and such

  15. Ethanol activation of protein kinase A regulates GABA-A receptor subunit expression in the cerebral cortex and contributes to ethanol-induced hypnosis

    Directory of Open Access Journals (Sweden)

    Sandeep eKumar

    2012-04-01

    Full Text Available Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking and synaptic excitability. Both protein kinase C (PKC and A (PKA are involved in regulation of γ-aminobutyric acid type A (GABA-A receptors through phosphorylation. However, the role of PKA in regulating GABA-A receptors following acute ethanol exposure is not known. The present study investigated the role of PKA in ethanol effects on GABA-A receptor α1 subunit expression in the P2 synaptosomal fraction of the rat cerebral cortex. Additionally, GABA-related behaviors were also examined. Rats were administered ethanol (2.0 – 3.5 g/kg or saline and PKC, PKA and GABA-A receptor α1 subunit levels were measured by Western blot analysis. Ethanol (3.5 g/kg transiently increased GABA-A receptor α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, the moderate ethanol dose (2.0g/kg had no effect on GABA-A α1 subunit levels although PKA RIIα and RIIβ were increased at 10 and 60 minutes, when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABA-A α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABA-A receptor α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex duration. This effect appears to be mediated in part by GABA-A receptors as increasing PKA activity also increased the duration of muscimol-induced loss of righting reflex. Overall these data suggest that PKA mediates ethanol-induced GABA-A receptor expression and contributes to ethanol behavioral effects involving GABA-A receptors.

  16. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

    Science.gov (United States)

    Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

    2015-09-01

    To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

  17. Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress.

    Science.gov (United States)

    Deguchi, Kentaro; Hayashi, Takeshi; Nagotani, Shoko; Sehara, Yoshihide; Zhang, Hanzhe; Tsuchiya, Atsushi; Ohta, Yasuyuki; Tomiyama, Koji; Morimoto, Nobutoshi; Miyazaki, Masahiro; Huh, Nam-Ho; Nakao, Atsunori; Kamiya, Tatsushi; Abe, Koji

    2008-01-10

    Biliverdin (BV), one of the byproducts of heme catalysis through heme oxygenase (HO) system, is a scavenger of reactive oxygen species (ROS). We hypothesized that BV treatment could protect rat brain cells from oxidative injuries via its anti-oxidant efficacies. Cerebral infarction was induced by transient middle cerebral artery occlusion (tMCAO) for 90 min, followed by reperfusion. BV or vehicle was administered intraperitoneally immediately after reperfusion. The size of the cerebral infarction 2 days after tMCAO was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Superoxide generation 4 h after tMCAO was determined by detection of oxidized hydroethidine. In addition, the oxidative impairment of neurons were immunohistochemically assessed by stain for lipid peroxidation with 4-hydroxy-2-nonenal (4-HNE) and damaged DNA with 8-hydroxy-2'-deoxyguanosine (8-OHdG). BV treatment significantly reduced infarct volume of the cerebral cortices associated with less superoxide production and decreased oxidative injuries of brain cells. The present study demonstrated that treatment with BV ameliorated the oxidative injuries on neurons and decreased brain infarct size in rat tMCAO model.

  18. Cerebral arterial bolus arrival time is prolonged in multiple sclerosis and associated with disability.

    Science.gov (United States)

    Paling, David; Thade Petersen, Esben; Tozer, Daniel J; Altmann, Daniel R; Wheeler-Kingshott, Claudia A M; Kapoor, Raju; Miller, David H; Golay, Xavier

    2014-01-01

    Alterations in the overall cerebral hemodynamics have been reported in multiple sclerosis (MS); however, their cause and significance is unknown. While potential venous causes have been examined, arterial causes have not. In this study, a multiple delay time arterial spin labeling magnetic resonance imaging sequence at 3T was used to quantify the arterial hemodynamic parameter bolus arrival time (BAT) and cerebral blood flow (CBF) in normal-appearing white matter (NAWM) and deep gray matter in 33 controls and 35 patients with relapsing-remitting MS. Bolus arrival time was prolonged in MS in NAWM (1.0±0.2 versus 0.9±0.2 seconds, P=0.031) and deep gray matter (0.90±0.18 versus 0.80±0.14 seconds, P=0.001) and CBF was increased in NAWM (14±4 versus 10±2 mL/100 g/min, P=0.001). Prolonged BAT in NAWM (P=0.042) and deep gray matter (P=0.01) were associated with higher expanded disability status score. This study demonstrates alteration in cerebral arterial hemodynamics in MS. One possible cause may be widespread inflammation. Bolus arrival time was longer in patients with greater disability independent of atrophy and T2 lesion load, suggesting alterations in cerebral arterial hemodynamics may be a marker of clinically relevant pathology.

  19. Migraine pain associated with middle cerebral artery dilatation

    DEFF Research Database (Denmark)

    Friberg, L; Olesen, J; Iversen, H K

    1991-01-01

    returned to normal after treatment with sumatriptan and recovery. Since rCBF in the MCA supply territory was unaffected, the lower velocity can be explained only by dilatation of the MCA. The mean MCA diameter increase was estimated to be 20%. Thus, headache was associated with intracranial large arterial...

  20. Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorder

    NARCIS (Netherlands)

    Vállez García, David; Otte, A.; Willemsen, A. T. M.; Dierckx, R. A. J. O.; Doorduin, J.; Hostege, G.

    2015-01-01

    Aim: Whiplash trauma in one of the most frequent consequencesof motor vehicle accidents. While initial symptoms resolve withina few weeks in many cases, some patients develop persistentsymptoms that include pain, headache, visual, and/or psychologicaldisturbances, termed as Whiplash-associated

  1. The Rare Association of Moyamoya Disease and Cerebral Arteriovenous Malformations: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Te Chang [Chi-Mei Foundation Hospital, Tainan (China); Guo, Wan Yuo; Wu, Hsiu Mei; Chang, Feng Chi; Shiau, Cheng Ying; Chung, Wen Yuh [Taipei Veterans General Hospital, Taipei (China)

    2008-07-15

    A 36-year-old man was diagnosed with a right temporal lobe grade II cerebral arteriovenous malformation (cAVM) and was treated with radiosurgery. At nine months after the cAVM radiosurgery, the patient began to develop bilateral focal narrowing at the M1 segments of the bilateral middle cerebral arteries. The narrowing progressively deteriorated as was demonstrated on longitudinal serial follow- up MR imaging. X-ray angiography performed at 51 months after radiosurgery confirmed that the cAVM was cured and a diagnosis of moyamoya disease. To the best of our knowledge, this is the first case of cAVM-associated moyamoya disease that developed after radiosurgery. Given the chronological sequence of disease development and radiation dose distribution of radiosurgery, it is proposed that humoral or unknown predisposing factors, rather than direct radiation effects, are the cause of moyamoya disease associated with cAVM.

  2. Neural associations of the early retinotopic cortex with the lateral occipital complex during visual perception.

    Directory of Open Access Journals (Sweden)

    Delong Zhang

    Full Text Available Previous studies have demonstrated that the early retinotopic cortex (ERC, i.e., V1/V2/V3 is highly associated with the lateral occipital complex (LOC during visual perception. However, it remains largely unclear how to evaluate their associations in quantitative way. The present study tried to apply a multivariate pattern analysis (MVPA to quantify the neural activity in ERC and its association with that of the LOC when participants saw visual images. To this end, we assessed whether low-level visual features (Gabor features could predict the neural activity in the ERC and LOC according to a voxel-based encoding model (VBEM, and then quantified the association of the neural activity between these regions by using an analogical VBEM. We found that the Gabor features remarkably predicted the activity of the ERC (e.g., the predicted accuracy was 52.5% for a participant instead of that of the LOC (4.2%. Moreover, the MVPA approach can also be used to establish corresponding relationships between the activity patterns in the LOC and those in the ERC (64.2%. In particular, we found that the integration of the Gabor features and LOC visual information could dramatically improve the 'prediction' of ERC activity (88.3%. Overall, the present study provides new evidences for the possibility of quantifying the association of the neural activity between the regions of ERC and LOC. This approach will help to provide further insights into the neural substrates of the visual processing.

  3. Cerebral activation associated with sexual arousal in response to a pornographic clip: A 15O-H2O PET study in heterosexual men.

    Science.gov (United States)

    Bocher, M; Chisin, R; Parag, Y; Freedman, N; Meir Weil, Y; Lester, H; Mishani, E; Bonne, O

    2001-07-01

    This study attempted to use PET and 15O-H2O to measure changes in regional cerebral blood flow (rCBF) during sexual arousal evoked in 10 young heterosexual males while they watched a pornographic video clip, featuring heterosexual intercourse. This condition was compared with other mental setups evoked by noisy, nature, and talkshow audiovisual clips. Immediately after each clip, the participants answered three questions pertaining to what extent they thought about sex, felt aroused, and sensed an erection. They scored their answers using a 1 to 10 scale. SPM was used for data analysis. Sexual arousal was mainly associated with activation of bilateral, predominantly right, inferoposterior extrastriate cortices, of the right inferolateral prefrontal cortex and of the midbrain. The significance of those findings is discussed in the light of current theories concerning selective attention, "mind reading" and mirroring, reinforcement of pleasurable stimuli, and penile erection.

  4. Association of Cerebral Amyloidosis, Blood Pressure, and Neuronal Injury with Late-life Onset Depression

    Directory of Open Access Journals (Sweden)

    Min Soo Byun

    2016-10-01

    Full Text Available Previous literature suggests that Alzheimer’s disease (AD process may contribute to late-life onset depression (LLOD. Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC. Comorbid mild cognitive impairment (MCI was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLODMCI showed increased cerebral 11C-Pittsburg compound B (PiB retention and plasma beta-amyloid 1-40 and 1-42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI. LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM density, cerebral amyloidosis and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes—SBP elevation, in particular—are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals.

  5. Cost of Treatment of Cerebral Aneurysm Embolization: Study of Associated Factors

    OpenAIRE

    Cheikh, Amine; Rachid, Razine; Jehanne, Aasfara; Adil, Ababou; Ali, Benomar; Cherrah, Yahya; Amine, El Hassani; Abdeljalil, El Quessar

    2016-01-01

    Background Surgical clipping or endovascular coiling are the main procedures used in the treatment of cerebral aneurysms, with a preference for endovascular coiling. In Morocco, the number of patients needing endovascular coiling is growing, but many of them do not have access to this technique. The aim of this study was to determine the main parameters associated with variations in the total cost of this procedure in order to establish the amount (lump sum) that may be reimbursed by health i...

  6. Haemophilus parainfluenzae Endocarditis Associated With Maxillary Sinusitis and Complicated by Cerebral Emboli in a Young Man.

    Science.gov (United States)

    Duzenli, Anthony E; Dwyer, John; Carey, Jeanne

    2017-01-01

    HACEK endocarditis is often difficult to diagnose given the slow-growing characteristics of the organisms involved. Haemophilus parainfluenzae, one of the HACEK organisms, is an uncommon cause of endocarditis. We describe a case of a previously healthy young man with H parainfluenzae endocarditis that was associated with maxillary sinusitis and severe systemic complications, including septic cerebral emboli and mitral valve perforation. Previously reported cases have also described a predilection for younger people, cardiac valve pathology, and a high prevalence of stroke.

  7. Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

    Science.gov (United States)

    Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

    2017-03-22

    Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that

  8. Cerebral oxygenation and hyperthermia

    Directory of Open Access Journals (Sweden)

    Anthony Richard Bain

    2014-03-01

    Full Text Available Hyperthermia is associated with marked reductions in cerebral blood flow (CBF. Increased distribution of cardiac output to the periphery, increases in alveolar ventilation and resultant hypocapnia each contribute to the fall in CBF during passive hyperthermia; however, their relative contribution remains a point of contention, and probably depends on the experimental condition (e.g. posture and degree of hyperthermia. The hyperthermia-induced hyperventilatory response reduces arterial CO2 pressure (PaCO2 causing cerebral vasoconstriction and subsequent reductions in flow. During supine passive hyperthermia, the majority of recent data indicate that reductions in PaCO2 may be the primary, if not sole, culprit for reduced CBF. On the other hand, during more dynamic conditions (e.g. hemorrhage or orthostatic challenges, an inability to appropriately decrease peripheral vascular conductance presents a condition whereby adequate cerebral perfusion pressure may be compromised secondary to reductions in systemic blood pressure. Although studies have reported maintenance of pre-frontal cortex oxygenation (assessed by near-infrared spectroscopy during exercise and severe heat stress, the influence of cutaneous blood flow is known to contaminate this measure. This review discusses the governing mechanisms associated with changes in CBF and oxygenation during moderate to severe (i.e. 1.0°C to 2.0°C increase in body core temperature levels of hyperthermia. Future research directions are provided.

  9. Abces cerebral associe a une cardiopathie congenitale cyanogene ...

    African Journals Online (AJOL)

    Introduction: La tétralogie de Fallot est la plus fréquente des cardiopathies congénitales cyanogènes. Elle représente près de 8% de l'ensemble des cardiopathies congénitales et peut être compliquée d'une suppuration intracrânienne. Le but de notre travail est de rapporter 3 cas d'abcès cérébral associés à cette ...

  10. Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

    Science.gov (United States)

    Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

    2015-08-30

    Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations.

    Science.gov (United States)

    Khundakar, Ahmad A; Hanson, Peter S; Erskine, Daniel; Lax, Nichola Z; Roscamp, Joseph; Karyka, Evangelia; Tsefou, Eliona; Singh, Preeti; Cockell, Simon J; Gribben, Andrew; Ramsay, Lynne; Blain, Peter G; Mosimann, Urs P; Lett, Deborah J; Elstner, Matthias; Turnbull, Douglass M; Xiang, Charles C; Brownstein, Michael J; O'Brien, John T; Taylor, John-Paul; Attems, Johannes; Thomas, Alan J; McKeith, Ian G; Morris, Christopher M

    2016-06-30

    Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.

  12. Association of cerebral palsy with Apgar score in low and normal birthweight infants: population based cohort study.

    Science.gov (United States)

    Lie, Kari Kveim; Grøholt, Else-Karin; Eskild, Anne

    2010-10-06

    To assess the association of Apgar score 5 minutes after birth with cerebral palsy in both normal weight and low birthweight children, and also the association with the cerebral palsy subdiagnoses of quadriplegia, diplegia, and hemiplegia. Population based cohort study. The Medical Birth Registry of Norway was used to identify all babies born between 1986 and 1995. These data were linked to the Norwegian Registry of Cerebral Palsy in Children born 1986-95, which was established on the basis of discharge diagnoses at all paediatric departments in Norway. All singletons without malformations born in Norway during 1986-95 and who survived the first year of life (n=543 064). Cerebral palsy diagnosed before the age of 5 years. 988 children (1.8 in 1000) were diagnosed with cerebral palsy before the age of 5 years. In total, 11% (39/369) of the children with Apgar score of less than 3 at birth were diagnosed with cerebral palsy, compared with only 0.1% (162/179 515) of the children with Apgar score of 10 (odds ratio (OR) 53, 95% CI 35 to 80 after adjustment for birth weight). In children with a birth weight of 2500 g or more, those with an Apgar score of less than 4 were much more likely to have cerebral palsy than those who had an Apgar score of more than 8 (OR 125, 95% confidence interval 91 to 170). The corresponding OR in children weighing less than 1500 g was 5 (95% CI 2 to 9). Among children with Apgar score of less than 4, 10-17% in all birthweight groups developed cerebral palsy. Low Apgar score was strongly associated with each of the three subgroups of spastic cerebral palsy, although the association was strongest for quadriplegia (adjusted OR 137 for Apgar score Apgar score >8, 95% CI 77 to 244). Low Apgar score was strongly associated with cerebral palsy. This association was high in children with normal birth weight and modest in children with low birth weight. The strength of the association differed between subgroups of spastic cerebral palsy. Given

  13. Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Kiyonori Ito

    Full Text Available Patients undergoing hemodialysis (HD often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2 was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients.Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan.The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p <0.001. Multiple regression analysis showed that cerebral rSO2 independently associated with pH (standardized coefficient: -0.35, HD duration (standardized coefficient: -0.33, and serum albumin concentration (standardized coefficient: 0.28. Furthermore, the rSO2 was significantly lower in HD patients with diabetes mellitus (DM, compared with patients without DM (46.8 ± 1.7% vs. 52.1 ± 1.8%, p <0.05.In HD patients, cerebral rSO2 was affected by multiple factors, including pH, HD duration, and serum albumin concentration. Furthermore, this is the first report describing significantly lower levels of rSO2 in HD patients with DM than in those without DM.

  14. Serum S100B protein could help to detect cerebral complications associated with extracorporeal membrane oxygenation (ECMO).

    Science.gov (United States)

    Nguyen, Duc Nam; Huyghens, Luc; Wellens, Francis; Schiettecatte, Johan; Smitz, Johan; Vincent, Jean-Louis

    2014-06-01

    To investigate if serum S100B protein levels could early detect cerebral complications under treatment extracorporeal membrane oxygenation (ECMO). Serum S100B levels were measured over 5 days in 32 patients with cardiogenic and septic shock, including 15 patients who treated by ECMO and 17 who did not. Cerebral complications included hemorrhage, stroke, encephalopathy with myoclonus, and brain death. Delirium was identified by the positive Confusion Assessment Method in the ICU. S100B levels were elevated in 24/32 patients (75 %) at ICU admission. Five patients developed cerebral complications (2 hemorrhages with 1 brain death, 1 encephalopathy with myoclonus in the ECMO group and 2 strokes in the non-ECMO group). At day 5, S100B levels were higher in the 5 patients with cerebral complications than in the 27 without cerebral complications, regardless of ECMO (0.426 [0.421, 0.652] vs. 0.102 [0.085, 0.135] μg/L, p = 0.011). S100B levels were also more elevated in 3 patients with than in 12 without cerebral complications associated with ECMO (0.799 [0.325, 0.965] vs. 0.102 [0.09, 0.607] μg/L, p = 0.033). S100B levels were not associated with delirium after sedation withdrawal. Measurement serum S100B could be useful to detect cerebral complications in deeply sedated patients associated with ECMO but not for monitoring delirium after sedation withdrawal.

  15. Advances in radiofrequency ablation of the cerebral cortex in primates using the venous system: Improvements for treating epilepsy with catheter ablation technology.

    Science.gov (United States)

    Henz, Benhur D; Friedman, Paul A; Bruce, Charles J; Holmes, David R; Bower, Mark; Madhavan, Malini; DeSimone, Christopher V; Wahnschaffe, Douglas; Berhow, Steven; Danielsen, Andrew J; Ladewig, Dorothy J; Mikell, Susan B; Johnson, Susan B; Suddendorf, Scott H; Kara, Tomas; Worrell, Gregory A; Asirvatham, Samuel J

    2014-08-01

    Pharmacology frequently fails for the treatment of epilepsy. Although surgical techniques are effective, these procedures are highly invasive. We describe feasibility and efficacy of minimally invasive mapping and ablation for the treatment of epilepsy. Mapping and radiofrequency ablations were performed via the venous system in eleven baboons and three dogs. Mapping in deep cerebral areas was obtained in all animals. High-frequency pacing was able to induce seizure activity of local cerebral tissue in 72% of our attempts. Cerebral activity could be seen during mapping. Ablative lesions were deployed at deep brain sites without steam pops or sudden impedance rise. Histologic analysis showed necrosis at the sites of ablation in all primates. Navigation through the cerebral venous system to map seizure activity is feasible. Radiofrequency energy can be delivered transvenously or transcortically to successfully ablate cortical tissue in this animal model using this innovative approach. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Regional cerebral blood flow changes associated with transcranial magnetic stimulation in refractory depressed patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, C. H.; Chung, Y. A.; Chae, J. H.; Oh, J. H.; Kim, S. H.; Sohn, H. S.; Chung, S. K. [The Catholic University of Korea, Seoul (Korea, Republic of)

    2005-07-01

    Imaging studies by repetitive transcranial magnetic stimulation (rTMS) demonstrates biological activities of the brain. The aim of this study was to investigate the patterns of regional cerebral blood flow (rCBF) after a series of therapeutic rTMS sessions. Nine patients with refractory depression who had not been responsive to appropriate pharmacotherapy over 1 year were randomly assigned to daily 1 Hz right-sided rTMS or 20 Hz left-sided rTMS sessions for over 3 weeks. Baseline and 3-week post-rTMS treatment SPECT images were obtained 40 minutes after intravenous injection of approximately 740925 MBq of Tc-99m ECD using a multi-detector scanner (ECAM plus; Siemens, Erlangen, Germany) equipped with a low-energy, fan-beam collimator. All patients showed a good clinical outcome. Statistically significant common increase in rCBF patterns was found in the fusiform gyrus of left temporal lobe, left hippocampus, left superior parietal lobule, superior frontal gyrus of right frontal lobe, right lateral globus pallidus and cingulated gyrus of both limbic lobes. And in the fusiform gyrus of left occipital lobe and middle frontal gyrus of right frontal lobe decreased uptake was seen compared to controls. Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased activity in specific brain regions in patients with treatment refractory depression. Therapeutic TMS seems to influence distinct cortical regions, as well as different pathways, affecting rCBF in a homogeneous manner that is probably region dependent and illness related.

  17. Cerebral Ventriculitis Associated with Otogenic Meningoencephalitis in a Dog.

    Science.gov (United States)

    Wu, Chih-Ching; Chang, Ya-Pei

    2015-01-01

    A dog was evaluated for rapidly progressive mentation change, ataxia, and tetraparesis. The dog's neurological status deteriorated drastically. It became comatose with bilateral mydriasis, and the pupillary light reflex was absent. An anti-inflammatory dose of methylprednisolone was administered, and temporary stabilization of neurological status was achieved. MRI findings were suggestive of ventriculitis and meningoencephalitis originating from the left tympanic cavity. A gadolinium leakage phenomenon was noted, likely resulting from severe damage to the blood-cerebrospinal fluid barrier during the inflammatory process. Analysis of the cerebrospinal fluid and materials in the left tympanic cavity further confirmed the diagnosis. Following surgical and antibiotic treatment, the dog recovered well with only a mild residual head tilt. Seven months after surgery, the dog had a recurrent infection of the left tympanic cavity without intracranial involvement. A second surgery led to an uneventful recovery, and the dog was clinically normal except for a mild head tilt 3 yr after the initial presentation. This is the first report describing ventriculitis associated with otogenic meningoencephalitis in dogs and a gadolinium leakage phenomenon displayed on MRI. The long-term outcome of ventriculitis-complicated otogenic meningoencephalitis in dogs could be satisfied with prompt diagnosis and treatment.

  18. Cerebral Arterial Variations Associated with Moyamoya Disease Diagnosed by MR Angiography.

    Science.gov (United States)

    Uchino, Akira; Saito, Naoko; Takahashi, Masahiro; Kurita, Hiroki; Ishihara, Shoichiro

    2014-12-01

    Moyamoya disease is a rare progressive cerebrovascular steno-occlusive disease associated with different variations of the cerebral arteries. We evaluated the types and prevalence of such variations among patients with moyamoya disease. In our institution during the past seven years, we diagnosed 72 patients (24 male, 48 female; aged 6 to 75 years, mean, 42 years) with moyamoya disease by magnetic resonance (MR) angiography using either a 3-Tesla or one of two 1.5-T imagers and a standard time-of-flight technique without contrast media. An experienced neuroradiologist retrospectively reviewed the images. There were 15 cerebral arterial variations in 13 of 72 patients with moyamoya disease (18.1%), including four basilar artery fenestrations, three ophthalmic arteries arising from the middle meningeal artery, two intracranial vertebral artery fenestrations, two persistent first cervical intersegmental arteries, two persistent trigeminal arteries, one extracranial origin of the posterior inferior cerebellar artery, and one persistent stapedial artery. Although our number of patients was small, moyamoya disease was frequently associated with variations of the cerebral arteries, especially fenestrations in the vertebrobasilar system and persistent trigeminal artery.

  19. Protective effect of ginkgo proanthocyanidins against cerebral ischemia/reperfusion injury associated with its antioxidant effects

    Directory of Open Access Journals (Sweden)

    Wang-li Cao

    2016-01-01

    Full Text Available Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proanthocyanidins (20, 40, 80 mg/kg were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and decrease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins (40 mg/kg confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatment of cerebral ischemia/reperfusion injury. Our results suggest that ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties.

  20. Cerebral Arterial Air Embolism Associated with Mechanical Ventilation and Deep Tracheal Aspiration

    Directory of Open Access Journals (Sweden)

    S. Gursoy

    2012-01-01

    Full Text Available Arterial air embolism associated with pulmonary barotrauma has been considered a rare but a well-known complication of mechanical ventilation. A 65-year-old man, who had subarachnoid hemorrhage with Glasgow coma scale of 8, was admitted to intensive care unit and ventilated with the help of mechanical ventilator. Due to the excessive secretions, deep tracheal aspirations were made frequently. GCS decreased from 8–10 to 4-5, and the patient was reevaluated with cranial CT scan. In CT scan, air embolism was detected in the cerebral arteries. The patient deteriorated and spontaneous respiratory activity lost just after the CT investigation. Thirty minutes later cardiac arrest appeared. Despite the resuscitation, the patient died. We suggest that pneumonia and frequent tracheal aspirations are predisposing factors for cerebral vascular air embolism.

  1. Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy.

    Directory of Open Access Journals (Sweden)

    Wei-Che Lin

    Full Text Available Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI and diffusion tensor imaging (DTI. Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC of the default mode network (DMN was determined by rs-fMRI, while the corresponding mean diffusivity (MD was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from "without HE" or "minimal HE" to "overt HE", correlated with decreased anterior-posterior fc-CC in DMN [F(4.415, p = 0.000]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.

  2. Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study.

    Science.gov (United States)

    Sydykova, Djyldyz; Stahl, Robert; Dietrich, Olaf; Ewers, Michael; Reiser, Maximilian F; Schoenberg, Stefan O; Möller, Hans-Jürgen; Hampel, Harald; Teipel, Stefan J

    2007-10-01

    Regional cortical atrophy in Alzheimer's disease (AD) most likely reflects the loss of cortical neurons. Several diffusion tensor imaging studies reported reduced fractional anisotropy (FA) in the corpus callosum in AD. The aim of this study was to investigate the association between reduced FA in the corpus callosum and gray matter atrophy in AD. Thirteen patients with AD with a mean (+/-standard deviation) age of 68.3 years (+/-11.5) and mean Mini Mental State Examination (MMSE) score of 21.8 (+/-4.8) were recruited. There were 13 control subjects with a mean age of 66.7 years (+/-6.4) and MMSE of 29.1 (+/-0.7). We used voxel-based morphometry of gray matter maps and region of interest-based analysis of FA in the corpus callosum. FA values of the anterior corpus callosum in AD patients were significantly correlated with gray matter volume in the prefrontal cortex and left parietal lobes. FA values of the posterior corpus callosum were significantly correlated with gray matter volume in the bilateral frontal, temporal, right parietal, and occipital lobes. In control subjects, no correlations were detected. Our findings suggest that decline of FA in the corpus callosum may be related to neuronal degeneration in corresponding cortical areas.

  3. Cerebral venous sinus thrombosis associated with essential thrombocytosis in a pediatric patient.

    Science.gov (United States)

    Jensen, Ashley W; Tefferi, Ayalew; Arndt, Carola A S

    2007-03-01

    Essential thrombocytosis (ET) is an uncommon pediatric hematologic disorder that can result in thrombotic complications, including cerebral venous sinus thrombosis (CVST). Although CVST associated with ET is exceedingly rare, it can be devastating to the patient. We here report a pediatric case of CVST associated with ET. The patient was treated with hydroxyurea and warfarin, which was later replaced by low-dose aspirin. Platelet counts were well controlled after 16 months of follow-up, and no further thrombotic events occurred. Mucositis was the main adverse effect of treatment.

  4. Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants

    DEFF Research Database (Denmark)

    Eriksen, Vibeke R; Hahn, Gitte H; Greisen, Gorm

    2014-01-01

    , but the anticipated difference in cerebral oxygenation was not detected. The need for mechanical ventilation in the first day of life and incidences of mortality was higher in the dopamine group. CONCLUSION: Dopamine therapy was associated with decreased CA in preterm infants. We were unable to determine whether......AIM: Hypotension is a common problem in newborn infants and is associated with increased mortality and morbidity. Dopamine is the most commonly used antihypotensive drug therapy, but has never been shown to improve neurological outcomes. This study tested our hypothesis that dopamine affects...

  5. Associations between total cerebral blood flow and age related changes of the brain.

    Directory of Open Access Journals (Sweden)

    Adriaan C G M van Es

    Full Text Available BACKGROUND AND PURPOSE: Although total cerebral blood flow (tCBF is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF is related to white matter hyperintensity (WMH volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow. MATERIALS AND METHODS: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min. RESULTS: We found a significant correlation between tCBF in mL/min and both age (r = -.124; p = passociation between tCBF in mL/min and %-atrophy (r = -.077; p = .103 or total WMH volume (r = -.069; p = .148. When tCBF was expressed in mL/100 mL/min the correlation between tCBF and age was no longer found (r = -.001; p = .985. Multivariate regression analyses corrected for age showed a significant correlation between tCBF in mL/100 mL/min and WMH volume (r = -.106; p = .044. No significant association between tCBF in mL/100 mL/min and %-atrophy was found. CONCLUSION: From this study we conclude that, when evaluating tCBF alterations due to various pathologies, tCBF should in mL/100 mL/min instead of mL/min. Furthermore, changes or differences in WMH volume should be accounted for.

  6. [Telemetry EEG of parietal association cortex in heroin-induced CPP rats].

    Science.gov (United States)

    Pan, Qun-Wan; Zhu, Zai-Man; Li, Jing; Li, Min; Zhou, Hong-Min

    2014-01-01

    To determine the relationship between EEG changes of parietal association cortex (PtA) and drug-seeking behaviors of heroin-induced conditioned place preference (CPP) rats. Stereotaxic electrode was buried in the PtA of rats, which were then divided randomly into heroin-induced CPP group and operation-only control group. A CPP video system in combination with EEG wireless telemetry was used for recording PtA EEG and the behaviors of the rats-staying in black or white chamber of the video box; shuttling between black-white chambers or between white-black chambers. No significant difference in percentage of the telemetry EEG waves was found between the two groups of rats when they stayed in the black or white chambers. The heroin-induced CPP rats had increased percentage of delta waves (P rats shuttled between white-black chambers. EEG changes on PtA of heroin-induced CPP rats differ between staying and shuttling states. Such changes may not be associated with drug-seeking behaviors.

  7. Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis.

    Science.gov (United States)

    Olsen, Rosanna K; Yeung, Lok-Kin; Noly-Gandon, Alix; D'Angelo, Maria C; Kacollja, Arber; Smith, Victoria M; Ryan, Jennifer D; Barense, Morgan D

    2017-09-01

    We investigated whether older adults without subjective memory complaints, but who present with cognitive decline in the laboratory, demonstrate atrophy in medial temporal lobe (MTL) subregions associated with Alzheimer's disease. Forty community-dwelling older adults were categorized based on Montreal Cognitive Assessment (MoCA) performance. Total gray/white matter, cerebrospinal fluid, and white matter hyperintensity load were quantified from whole-brain T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging scans, whereas hippocampal subfields and MTL cortical subregion volumes (CA1, dentate gyrus/CA2/3, subiculum, anterolateral and posteromedial entorhinal, perirhinal, and parahippocampal cortices) were quantified using high-resolution T2-weighted scans. Cognitive status was evaluated using standard neuropsychological assessments. No significant differences were found in the whole-brain measures. However, MTL volumetry revealed that anterolateral entorhinal cortex (alERC) volume-the same region in which Alzheimer's pathology originates-was strongly associated with MoCA performance. This is the first study to demonstrate that alERC volume is related to cognitive decline in undiagnosed community-dwelling older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior.

    Science.gov (United States)

    Chen, Hao; Wang, Yi-jie; Yang, Li; Sui, Jian-feng; Hu, Zhi-an; Hu, Bo

    2016-02-16

    Associative learning is thought to require coordinated activities among distributed brain regions. For example, to direct behavior appropriately, the medial prefrontal cortex (mPFC) must encode and maintain sensory information and then interact with the cerebellum during trace eyeblink conditioning (TEBC), a commonly-used associative learning model. However, the mechanisms by which these two distant areas interact remain elusive. By simultaneously recording local field potential (LFP) signals from the mPFC and the cerebellum in guinea pigs undergoing TEBC, we found that theta-frequency (5.0-12.0 Hz) oscillations in the mPFC and the cerebellum became strongly synchronized following presentation of auditory conditioned stimulus. Intriguingly, the conditioned eyeblink response (CR) with adaptive timing occurred preferentially in the trials where mPFC-cerebellum theta coherence was stronger. Moreover, both the mPFC-cerebellum theta coherence and the adaptive CR performance were impaired after the disruption of endogenous orexins in the cerebellum. Finally, association of the mPFC -cerebellum theta coherence with adaptive CR performance was time-limited occurring in the early stage of associative learning. These findings suggest that the mPFC and the cerebellum may act together to contribute to the adaptive performance of associative learning behavior by means of theta synchronization.

  9. Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior

    Science.gov (United States)

    Chen, Hao; Wang, Yi-jie; Yang, Li; Sui, Jian-feng; Hu, Zhi-an; Hu, Bo

    2016-01-01

    Associative learning is thought to require coordinated activities among distributed brain regions. For example, to direct behavior appropriately, the medial prefrontal cortex (mPFC) must encode and maintain sensory information and then interact with the cerebellum during trace eyeblink conditioning (TEBC), a commonly-used associative learning model. However, the mechanisms by which these two distant areas interact remain elusive. By simultaneously recording local field potential (LFP) signals from the mPFC and the cerebellum in guinea pigs undergoing TEBC, we found that theta-frequency (5.0–12.0 Hz) oscillations in the mPFC and the cerebellum became strongly synchronized following presentation of auditory conditioned stimulus. Intriguingly, the conditioned eyeblink response (CR) with adaptive timing occurred preferentially in the trials where mPFC-cerebellum theta coherence was stronger. Moreover, both the mPFC-cerebellum theta coherence and the adaptive CR performance were impaired after the disruption of endogenous orexins in the cerebellum. Finally, association of the mPFC -cerebellum theta coherence with adaptive CR performance was time-limited occurring in the early stage of associative learning. These findings suggest that the mPFC and the cerebellum may act together to contribute to the adaptive performance of associative learning behavior by means of theta synchronization. PMID:26879632

  10. Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

    Science.gov (United States)

    Ruan, Hongyu; Yao, Wei-Dong

    2017-01-25

    Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to

  11. Human regional cerebral blood flow during rapid-eye-movement sleep

    DEFF Research Database (Denmark)

    Madsen, P L; Holm, S; Vorstrup, S

    1991-01-01

    CBF increased by 4% (p less than 0.01) in the associative visual area, while it decreased by 9% (p less than 0.01) in the inferior frontal cortex. The CBF increase in the associative visual area suggests that activation of cerebral structures processing complex visual material is correlated to visual...... dream experiences. On the other hand, the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams....

  12. The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities—An Exploratory Study Using Multimodal Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Lin Shi

    2017-11-01

    Full Text Available White matter hyperintensities (WMHs have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC, were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

  13. The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities-An Exploratory Study Using Multimodal Magnetic Resonance Imaging.

    Science.gov (United States)

    Shi, Lin; Miao, Xinyuan; Lou, Wutao; Liu, Kai; Abrigo, Jill; Wong, Adrian; Chu, Winnie C W; Wang, Defeng; Mok, Vincent C T

    2017-01-01

    White matter hyperintensities (WMHs) have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF) and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC), were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

  14. Neuroticism and extraversion mediate the association between loneliness and the dorsolateral prefrontal cortex.

    Science.gov (United States)

    Kong, Xia; Wei, Dongtao; Li, Wenfu; Cun, Lingli; Xue, Song; Zhang, Qinglin; Qiu, Jiang

    2015-01-01

    Loneliness is an unpleasant and distressing feeling that a person experiences when he/she perceives that his/her social relationships are lacking in someway, either quantitatively or qualitatively; this can be linked to anxiety, depression, and suicide risk. Previous studies have found that certain personality traits (which are temporally stable and heritable) are predictors of loneliness. However, little empirical evidence is available on the brain structures associated with loneliness, as well as how personality traits impact the relationship between loneliness and brain structure. Thus, the current study used voxel-based morphometry to identify the brain structures underlying individual differences in loneliness (as measured by the UCLA Loneliness Scale) in a large sample, and then, applied multiple mediation analyses to explore the nature of the influence of personality traits on the relationship between loneliness and brain structure. The results showed that lonely individuals had greater regional gray matter volume in the left dorsolateral prefrontal cortex (DLPFC), which might reflect immature functioning in terms of emotional regulation. More importantly, we found that neuroticism and extraversion partially mediated the relationship between the left DLPFC and loneliness. In summary, through morphometric and multiple mediation analyses, this paper further validates the influence of both neuroticism and extraversion on loneliness.

  15. Reversal learning strategy in adolescence is associated with prefrontal cortex activation.

    Science.gov (United States)

    Boehme, Rebecca; Lorenz, Robert C; Gleich, Tobias; Romund, Lydia; Pelz, Patricia; Golde, Sabrina; Flemming, Eva; Wold, Andrew; Deserno, Lorenz; Behr, Joachim; Raufelder, Diana; Heinz, Andreas; Beck, Anne

    2017-01-01

    Adolescence is a critical maturation period for human cognitive control and executive function. In this study, a large sample of adolescents (n = 85) performed a reversal learning task during functional magnetic resonance imaging. We analyzed behavioral data using a reinforcement learning model to provide individually fitted parameters and imaging data with regard to reward prediction errors (PE). Following a model-based approach, we formed two groups depending on whether individuals tended to update expectations predominantly for the chosen stimulus or also for the unchosen one. These groups significantly differed in their problem behavior score obtained using the child behavior checklist (CBCL) and in a measure of their developmental stage. Imaging results showed that dorsolateral striatal areas covaried with PE. Participants who relied less on learning based on task structure showed less prefrontal activation compared with participants who relied more on task structure. An exploratory analysis revealed that PE-related activity was associated with pubertal development in prefrontal areas, insula and anterior cingulate. These findings support the hypothesis that the prefrontal cortex is implicated in mediating flexible goal-directed behavioral control. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Working memory training is associated with lower prefrontal cortex activation in a divergent thinking task.

    Science.gov (United States)

    Vartanian, O; Jobidon, M-E; Bouak, F; Nakashima, A; Smith, I; Lam, Q; Cheung, B

    2013-04-16

    Working memory (WM) training has been shown to lead to improvements in WM capacity and fluid intelligence. Given that divergent thinking loads on WM and fluid intelligence, we tested the hypothesis that WM training would improve performance and moderate neural function in the Alternate Uses Task (AUT)-a classic test of divergent thinking. We tested this hypothesis by administering the AUT in the functional magnetic resonance imaging scanner following a short regimen of WM training (experimental condition), or engagement in a choice reaction time task not expected to engage WM (active control condition). Participants in the experimental group exhibited significant improvement in performance in the WM task as a function of training, as well as a significant gain in fluid intelligence. Although the two groups did not differ in their performance on the AUT, activation was significantly lower in the experimental group in ventrolateral prefrontal and dorsolateral prefrontal cortices-two brain regions known to play dissociable and critical roles in divergent thinking. Furthermore, gain in fluid intelligence mediated the effect of training on brain activation in ventrolateral prefrontal cortex. These results indicate that a short regimen of WM training is associated with lower prefrontal activation-a marker of neural efficiency-in divergent thinking. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  17. Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex.

    Science.gov (United States)

    Rigucci, Silvia; Xin, Lijing; Klauser, Paul; Baumann, Philipp S; Alameda, Luis; Cleusix, Martine; Jenni, Raoul; Ferrari, Carina; Pompili, Maurizio; Gruetter, Rolf; Do, Kim Q; Conus, Philippe

    2018-01-01

    Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial. We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. [GlumPFC] was lower in EP users comparing to both HC and EP non-users (p working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. Cannabis use is associated with reduced prefrontal [GlumPFC] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.

  18. Slow pupillary light responses in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and neurological outcome.

    Science.gov (United States)

    Hamer, Elisa G; Vermeulen, R Jeroen; Dijkstra, Linze J; Hielkema, Tjitske; Kos, Claire; Bos, Arend F; Hadders-Algra, Mijna

    2016-12-01

    Having observed slow pupillary light responses (PLRs) in infants at high risk of cerebral palsy, we retrospectively evaluated whether these were associated with specific brain lesions or unfavourable outcomes. We carried out neurological examinations on 30 infants at very high risk of cerebral palsy five times until the corrected age of 21 months, classifying each PLR assessment as normal or slow. The predominant reaction during development was determined for each infant. Neonatal brain scans were classified based on the type of brain lesion. Developmental outcome was evaluated at 21 months of corrected age with a neurological examination, the Bayley Scales of Infant Development Second Edition and the Infant Motor Profile. Of the 30 infants, 16 developed cerebral palsy. Predominantly slow PLRs were observed in eight infants and were associated with periventricular leukomalacia (p = 0.007), cerebral palsy (p = 0.039), bilateral cerebral palsy (p = 0.001), poorer quality of motor behaviour (p slow PLR in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and poorer developmental outcome. Slow PLR might be an expression of white matter damage, resulting in dysfunction of the complex cortico-subcortical circuitries. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. Regional vulnerability of longitudinal cortical association connectivity: Associated with structural network topology alterations in preterm children with cerebral palsy.

    Science.gov (United States)

    Ceschin, Rafael; Lee, Vince K; Schmithorst, Vince; Panigrahy, Ashok

    2015-01-01

    Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL), are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI) studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4) and 75 healthy controls (mean age 5.7 ± 3.4). Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS) and voxel-based morphometry (VBM) demonstrating diffusely reduced fractional anisotropy (FA) reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1) reduced regional posterior-anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation) correlated with reduced posterior-anterior gradient of intra-regional (nodal efficiency) metrics with relative sparing of frontal and temporal regions; and (2) reduced regional FA within frontal-thalamic-striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract) correlated with

  20. Repeated anodal transcranial direct current stimulation induces neural plasticity-associated gene expression in the rat cortex and hippocampus.

    Science.gov (United States)

    Kim, Min Sun; Koo, Ho; Han, Sang Who; Paulus, Walter; Nitsche, Michael A; Kim, Yun-Hee; Yoon, Jin A; Shin, Yong-Il

    2017-01-01

    Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days. Levels of mRNA for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), synapsin I, Ca2+/calmodulin-dependent protein kinase II (CaMKII), activity-regulated cytoskeleton-associated protein (Arc), and c-Fos were analyzed using SYBR Green quantitative real-time polymerase chain reaction (PCR). We found that 7 days of unilateral A-tDCS resulted in significant increases in transcription of all plasticity-related genes tested in the ipsilateral cortex. Daily A-tDCS also resulted in a significant increase in c-Fos mRNA in the ipsilateral hippocampus. These results indicate that altered expression of plasticity-associated genes in the cortex and hippocampus is a molecular substrate of A-tDCS-induced neural plasticity.

  1. Childhood emotional maltreatment severity is associated with dorsal medial prefrontal cortex responsivity to social exclusion in young adults.

    Science.gov (United States)

    van Harmelen, Anne-Laura; Hauber, Kirsten; Gunther Moor, Bregtje; Spinhoven, Philip; Boon, Albert E; Crone, Eveline A; Elzinga, Bernet M

    2014-01-01

    Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.

  2. Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism.

    Directory of Open Access Journals (Sweden)

    Christina R Muratore

    Full Text Available The folate and vitamin B12-dependent enzyme methionine synthase (MS is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression.

  3. Haemophilus parainfluenzae Endocarditis Associated With Maxillary Sinusitis and Complicated by Cerebral Emboli in a Young Man

    Directory of Open Access Journals (Sweden)

    Anthony E. Duzenli MD

    2017-04-01

    Full Text Available HACEK endocarditis is often difficult to diagnose given the slow-growing characteristics of the organisms involved. Haemophilus parainfluenzae, one of the HACEK organisms, is an uncommon cause of endocarditis. We describe a case of a previously healthy young man with H parainfluenzae endocarditis that was associated with maxillary sinusitis and severe systemic complications, including septic cerebral emboli and mitral valve perforation. Previously reported cases have also described a predilection for younger people, cardiac valve pathology, and a high prevalence of stroke.

  4. Anti-NMDA receptor encephalitis associated with transient cerebral dyschromatopsia, prosopagnosia, and lack of stereopsis.

    Science.gov (United States)

    Sawamura, Hiromasa; Yamamoto, Tomotaka; Ohtomo, Ryo; Bannai, Taro; Wakakura, Masato; Tsuji, Shoji

    2014-06-01

    A 20-year-old woman suffered from anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and was treated with removal of an ovarian teratoma and retroperitoneal ganglioneuroma in addition to immunotherapy. She was incapable of face recognition, had difficulty with object recognition, and lacked color sensation and stereo perception during recovery. These symptoms were transient and completely resolved over 4 months. Our report documents additional aspects of visual impairment associated with anti-NMDAR encephalitis and suggests that the disease can lead to diffuse cerebral dysfunction including the cortical visual system.

  5. Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.

    Science.gov (United States)

    Roddy, Erika; Sear, Katherine; Felton, Erin; Tamrazi, Benita; Gauvain, Karen; Torkildson, Joseph; Buono, Benedict Del; Samuel, David; Haas-Kogan, Daphne A; Chen, Josephine; Goldsby, Robert E; Banerjee, Anuradha; Lupo, Janine M; Molinaro, Annette M; Fullerton, Heather J; Mueller, Sabine

    2016-11-01

    A specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors. In a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age tumor survivors treated with radiation. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. HELLP Syndrome and Cerebral Venous Sinus Thrombosis Associated with Factor V Leiden Mutation during Pregnancy

    Directory of Open Access Journals (Sweden)

    Zeynep Ozcan Dag

    2014-01-01

    Full Text Available Preeclampsia is a leading cause of maternal mortality and morbidity worldwide. The neurological complications of preeclampsia and eclampsia are responsible for a major proportion of the morbidity and mortality for women and their infants alike. Hormonal changes during pregnancy and the puerperium carry an increased risk of venous thromboembolism including cerebral venous sinus thrombosis (CVST. Factor 5 leiden (FVL is a procoagulant mutation associated primarily with venous thrombosis and pregnancy complications. We report a patient with FVL mutation who presented with CVST at 24th week of pregnancy and was diagnosed as HELLP syndrome at 34th week of pregnancy.

  7. The 'double cortex' syndrome on MRI.

    Science.gov (United States)

    Hashimoto, R; Seki, T; Takuma, Y; Suzuki, N

    1993-01-01

    We report a 6-year-old girl with diffuse subcortical heterotopia (band heterotopia), an unusual type of ectopic gray matter on magnetic resonance imaging (MRI). Her cerebral parenchyma had four layers consisting of cortex, thin outer white matter, diffuse subcortical heterotopia, and inner white matter around the lateral ventricles, giving the appearance of a 'double cortex'. The overlying cortex had midly broad gyri, especially in the frontal lobes. MRI showed the appearance of laminar heterotopia, a classical pathological entity. The double cortex syndrome is presumably a radiological delineation of laminar heterotopia. Her development was slightly delayed and she was clumsy and easily upset, with poor impulse control. However, her daily life was largely unaffected in spite of the severe abnormalities on MRI. She had abnormal movements during sleep, and sleeping EEG showed high voltage spindles in the bilateral frontal areas but no epileptic discharges. It could not be determined whether or not these movements were epileptic. The double cortex syndrome, an anomaly of the central nervous system associated with mental retardation, epilepsy, behavioral problems, and exclusive occurrence in girls, will be established as a clinico-radiological entity.

  8. Effects of chronic exposure to 950 MHz ultra-high-frequency electromagnetic radiation on reactive oxygen species metabolism in the right and left cerebral cortex of young rats of different ages.

    Science.gov (United States)

    Furtado-Filho, Orlando V; Borba, Juliana B; Maraschin, Tatiana; Souza, Larissa M; Henriques, João A P; Moreira, José C F; Saffi, Jenifer

    2015-01-01

    To assess the effect of 950 MHz ultra-high-frequency electromagnetic radiation (UHF-EMR) on biomarkers of oxidative damage to DNA, proteins and lipids in the left cerebral cortex (LCC) and right cerebral cortex (RCC) of neonate and 6-day-old rats. Twelve rats were equally divided into two groups as controls (CR) and exposed (ER), for each age (0 and 6 days). The LCC and RCC were examined in ER and CR after exposure. Radiation exposure lasted 30 min per day for up to 27 days (throughout pregnancy and 6 days postnatal). The specific absorption rate ranged from 1.32-1.14 W/kg. The damage to lipids, proteins and DNA was verified by thiobarbituric acid reactive substances, carbonylated proteins (CP) and comets, respectively. The concentration of glucose in the peripheral blood of the rats was measured by the Accu-Chek Active Kit due to increased CP in RCC. In neonates, no modification of the biomarkers tested was detected. On the other hand, there was an increase in the levels of CP in the RCC of the 6-day-old ER. Interestingly, the concentration of blood glucose was decreased in this group. Our results indicate that there is no genotoxicity and oxidative stress in neonates and 6 days rats. However, the RCC had the highest concentration of CP that do not seem to be a consequence of oxidative stress. This study is the first to demonstrate the use of UHF-EMR causes different damage responses to proteins in the LCC and RCC.

  9. State of cerebral hemodynamics in patients with cognitive dysfunction associated with atrial fibrillation

    Directory of Open Access Journals (Sweden)

    S.N. Stadnik

    2014-01-01

    Full Text Available The aim of the study was to cerebral hemodynamics in patients with cognitive dysfunction associated with atrial fibrillation (AF. Patients and methods. Fifty-six patients aged 40–75 years (the mean age was 62.7±6.3 years with nonvalvular AF caused by ischemic heart disease were examined. In 30 (53.6% patients AF was permanent; in 26 (46.4% patients, it was either persistent or paroxysmal. The exclusion criteria were as follows: past transient ischemic attacks, stroke or myocardial infarction, and severe somatic diseases. All patients with AF were evaluated for cognitive functions (using the short scale for assessing the mental status, auditory memory and associative memory (using the Schulte test, and emotional background (using the Hospital Anxiety and Depression Scale. Ultrasonography of the extracranial and intracranial vessels and registration of the average linear blood flow velocity (LBFV was performed. Results. Cognitive impairments (CI were diagnosed in 38 patients who entered the main group; patients with AF without CI comprised the control group. 82.6% of patients of the main group were diagnosed with constrictive lesion of the carotid (CA and vertebral (VA arteries of various severity; the isolated lesion of the CA was observed in 23.7% of patients, the isolated lesion of the VA in 18.4%; multiple lesions of the CA and VA in 69.4%; and the hemodynamically significant lesion, in 30.3%. In patients of the control group, constrictive lesions of the extracranial arteries were observed in 65.5% of cases. Condition of the major arteries of the head (MAH significantly affects the LBFV parameters of the intracranial arteries. In patients with multiple lesions of the CA and VA, the LBFV in the intracranial vessels was much lower than that in patients with isolated lesions of the CA and VA.The relation between the rate and severity of constrictive lesions of the MAH and the presence of AF accompanied with CI was noted in patients. Cerebral

  10. Survey on Types and Associated disorders of Cerebral Palsy in Eastern and Northern Districts of Tehran

    Directory of Open Access Journals (Sweden)

    Farin Soleimani

    2011-10-01

    Conclusion: In this study, unilateral - spastic cerebral palsy was found as the most common type. Therefore, more evaluation to determine the about etiology of this type of cerebral palsy in our population is necessary.

  11. Secondary decline of cerebral autoregulation is associated with worse outcome after intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Reinhard, Matthias; Neunhoeffer, Florian; Gerds, Thomas A

    2010-01-01

    and 5 after ictus. Autoregulation was noninvasively measured from spontaneous fluctuations of blood pressure and middle cerebral artery flow velocity (assessed by transcranial Doppler) using the correlation coefficient index Mx. From the same signals, non-invasive cerebral perfusion pressure...

  12. Factors associated with dental caries in the primary dentition of children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Luana Leal Roberto

    2012-10-01

    Full Text Available The aim of this study was to investigate factors associated with caries experience in the primary dentition of one- to five-year-old children with cerebral palsy. A total of 266 dental records were examined, and caries experience was measured by dmft. The following variables were also analyzed: gender, oral hygiene, history of gastroesophageal reflux, use of medications for gastroesophageal reflux, gingival status, sugar intake and reports of polyuria, excessive thirst and xerostomia. For analysis purposes, the individuals were categorized as those with and without caries experience and subcategorized into the following age groups: one year; two to three years; and four to five years. After bivariate analysis, variables with a p-value < 0.25 were selected for incorporation into the Poisson regression models. Considering the limitations of the protocol, the level of oral hygiene perceived on the first appointment was the only factor associated with caries experience among two-to-fiveyear-old children with cerebral palsy.

  13. Effect of serotonin on paired associative stimulation-induced plasticity in the human motor cortex.

    Science.gov (United States)

    Batsikadze, Giorgi; Paulus, Walter; Kuo, Min-Fang; Nitsche, Michael A

    2013-10-01

    Serotonin modulates diverse brain functions. Beyond its clinical antidepressant effects, it improves motor performance, learning and memory formation. These effects might at least be partially caused by the impact of serotonin on neuroplasticity, which is thought to be an important foundation of the respective functions. In principal accordance, selective serotonin reuptake inhibitors enhance long-term potentiation-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. As other neuromodulators have discernable effects on different kinds of plasticity in humans, here we were interested to explore the impact of serotonin on paired associative stimulation (PAS)-induced plasticity, which induces a more focal kind of plasticity, as compared with tDCS, shares some features with spike timing-dependent plasticity, and is thought to be relative closely related to learning processes. In this single-blinded, placebo-controlled, randomized crossover study, we administered a single dose of 20 mg citalopram or placebo medication and applied facilitatory- and excitability-diminishing PAS to the left motor cortex of 14 healthy subjects. Cortico-spinal excitability was explored via single-pulse transcranial magnetic stimulation-elicited MEP amplitudes up to the next evening after plasticity induction. After citalopram administration, inhibitory PAS-induced after-effects were abolished and excitatory PAS-induced after-effects were enhanced trendwise, as compared with the respective placebo conditions. These results show that serotonin modulates PAS-induced neuroplasticity by shifting it into the direction of facilitation, which might help to explain mechanism of positive therapeutic effects of serotonin in learning and medical conditions characterized by enhanced inhibitory or reduced facilitatory plasticity, including depression and stroke.

  14. Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.

    Science.gov (United States)

    Müller-Dahlhaus, Florian; Lücke, Caroline; Lu, Ming-Kuei; Arai, Noritoshi; Fuhl, Anna; Herrmann, Eva; Ziemann, Ulf

    2015-01-01

    Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed