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  1. Cerebral cortex modulation of pain

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    Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

    2009-01-01

    Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

  2. The Age of Human Cerebral Cortex Neurons

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    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.

  3. [Raman spectra of monkey cerebral cortex tissue].

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    Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

    2010-01-01

    Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

  4. Spindle Bursts in Neonatal Rat Cerebral Cortex

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    Jenq-Wei Yang

    2016-01-01

    Full Text Available Spontaneous and sensory evoked spindle bursts represent a functional hallmark of the developing cerebral cortex in vitro and in vivo. They have been observed in various neocortical areas of numerous species, including newborn rodents and preterm human infants. Spindle bursts are generated in complex neocortical-subcortical circuits involving in many cases the participation of motor brain regions. Together with early gamma oscillations, spindle bursts synchronize the activity of a local neuronal network organized in a cortical column. Disturbances in spindle burst activity during corticogenesis may contribute to disorders in cortical architecture and in the activity-dependent control of programmed cell death. In this review we discuss (i the functional properties of spindle bursts, (ii the mechanisms underlying their generation, (iii the synchronous patterns and cortical networks associated with spindle bursts, and (iv the physiological and pathophysiological role of spindle bursts during early cortical development.

  5. Spindle Bursts in Neonatal Rat Cerebral Cortex.

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    Yang, Jenq-Wei; Reyes-Puerta, Vicente; Kilb, Werner; Luhmann, Heiko J

    2016-01-01

    Spontaneous and sensory evoked spindle bursts represent a functional hallmark of the developing cerebral cortex in vitro and in vivo. They have been observed in various neocortical areas of numerous species, including newborn rodents and preterm human infants. Spindle bursts are generated in complex neocortical-subcortical circuits involving in many cases the participation of motor brain regions. Together with early gamma oscillations, spindle bursts synchronize the activity of a local neuronal network organized in a cortical column. Disturbances in spindle burst activity during corticogenesis may contribute to disorders in cortical architecture and in the activity-dependent control of programmed cell death. In this review we discuss (i) the functional properties of spindle bursts, (ii) the mechanisms underlying their generation, (iii) the synchronous patterns and cortical networks associated with spindle bursts, and (iv) the physiological and pathophysiological role of spindle bursts during early cortical development.

  6. Early GABAergic circuitry in the cerebral cortex.

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    Luhmann, Heiko J; Kirischuk, Sergei; Sinning, Anne; Kilb, Werner

    2014-06-01

    In the cerebral cortex GABAergic signaling plays an important role in regulating early developmental processes, for example, neurogenesis, migration and differentiation. Transient cell populations, namely Cajal-Retzius in the marginal zone and thalamic input receiving subplate neurons, are integrated as active elements in transitory GABAergic circuits. Although immature pyramidal neurons receive GABAergic synaptic inputs already at fetal stages, they are integrated into functional GABAergic circuits only several days later. In consequence, GABAergic synaptic transmission has only a minor influence on spontaneous network activity during early corticogenesis. Concurrent with the gradual developmental shift of GABA action from excitatory to inhibitory and the maturation of cortical synaptic connections, GABA becomes more important in synchronizing neuronal network activity.

  7. Emprego dos gangliosidos do cortex cerebral nas neuropatias perifericas

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    James Pitagoras De Mattos

    1981-12-01

    Full Text Available Os autores registram a experiência pessoal com o emprego de gangliosídios do cortex cerebral nas neuropatias periféricas. O ensaio clínico e eletromiográfico revelou-se eficaz em 30 dos 40 casos tratados. Enfatizam os melhores resultados em casos de paralisias faciais periféricas.

  8. A dynamic skull model for simulation of cerebral cortex folding.

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    Chen, Hanbo; Guo, Lei; Nie, Jingxin; Zhang, Tuo; Hu, Xintao; Liu, Tianming

    2010-01-01

    The mechanisms of human cerebral cortex folding and their interactions during brain development are largely unknown, partly due to the difficulties in biological experiments and data acquisition for the developing fetus brain. Computational modeling and simulation provide a novel approach to the understanding of cortex folding processes in normal or aberrant neurodevelopment. Based on our recently developed computational model of the cerebral cortex folding using neuronal growth model and mechanical skull constraint, this paper presents a computational dynamic model of the brain skull that regulates the cortical folding simulation. Our simulation results show that the dynamic skull model is more biologically realistic and significantly improves our cortical folding simulation results. This work provides further computational support to the hypothesis that skull is an important regulator of cortical folding.

  9. Radiation-induced apoptosis in developing fetal rat cerebral cortex

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    Chung, Woong Ki; Nam, Taek Keun; Lee, Min Cheol; Ahn, Sung Ja; Song, Ju Young; Park, Seung Jin; Nah, Byung Sik [College of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2003-09-01

    The study was performed to investigate apoptosis by radiation in the developing fetal rat brain. Fetal brains were irradiated in utero between the 17th and 19th days of fetal life(E17-19) by linear accelerator. A dose of irradiation ranging from 1 Gy to 4 Gy was used to evaluate dose dependency. To test time dependency the rats were irradiated with 2 Gy and then the fetal brain specimens were removed at variable time course; 1, 3, 6, 12 and 24 hours after the onset of irradiation. Immunohistochemical staining using in situ TdT-mediated dUTP nick end labelling (TUNEL) technique was used for apoptotic cells. The cerebral cortex, including three zones of cortical zone (CZ), intermediate zone (IZ), and ventricular zone (VZ), was examined. TUNEL positive cells revealed typical features of apoptotic cells under light microscope in the fetal rat cerebral cortex. Apoptotic cells were not found in the cerebral cortex of non-irradiated fetal rats, but did appear in the entire cerebral cortex after 1 Gy irradiation, and were more extensive at the ventricular and intermediate zones than at the cortical zone. The extent of apoptosis was increased with increasing doses of radiation. Apoptosis reached the peak at 6 hours after the onset of 2 Gy irradiation and persisted until 24 hours. Typical morphologic features of apoptosis by irradiation were observed in the developing fetal rat cerebral cortex. It was more extensive at the ventricular and intermediate zones than at the cortical zone, which suggested that stem cells or early differentiating cells are more radiosensitive than differentiated cells of the cortical zone.

  10. Microglia in the Cerebral Cortex in Autism

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    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…

  11. [Macro- and microscopic systematization of cerebral cortex malformations in children].

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    Milovanov, A P; Milovanova, O A

    2011-01-01

    For the first time in pediatric pathologicoanatomic practice the complete systematization of cerebral cortex malformations is represented. Organ, macroscopic forms: microencephaly, macroencephaly, micropolygyria, pachygyria, schizencephaly, porencephaly, lissencephaly. Histic microdysgenesis of cortex: type I includes isolated abnormalities such as radial (IA) and tangential (I B) subtypes of cortical dislamination; type II includes sublocal cortical dislamination with immature dysmorphic neurons (II A) and balloon cells (II B); type III are the combination focal cortical dysplasia with tuberous sclerosis of the hippocampus (III A), tumors (III B) and malformations of vessels, traumatic and hypoxic disorders (III C). Band heterotopias. Subependimal nodular heterotopias. Tuberous sclerosis. Cellular typification of cortical dysplasia: immature neurons and balloon cells.

  12. Proteomics analysis of cerebral cortex in Wistar rats

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    Xiaofeng ZHAO; Jingrong WEN; Shu WANG; Xuemin SHI

    2008-01-01

    To analyze the protein expression pattern of the cerebral cortex in Wistar rats using the proteomics approach, proteins were separated by two-dimensional gel electrophoresis, stained with Coomassie brilliant blue and digested with trypsin. Then, we analyzed the peptide section using a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and identified the protein by indexing special database (SwissProt) according to the finger printing of the peptide quality. Eighty-four protein spots were identified, includ-ing metabolic enzymes, skeleton proteins, heat shock pro-teins, antioxidant proteins, signaling proteins, proteasome related proteins, neuron and glial specific proteins and serum associated proteins. The result of this study enriches the database of the proteome in the cerebral cortex of rats and lays a foundation for further research of neurological disorders in rat models.

  13. Fate-restricted neural progenitors in the mammalian cerebral cortex.

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    Franco, Santos J; Gil-Sanz, Cristina; Martinez-Garay, Isabel; Espinosa, Ana; Harkins-Perry, Sarah R; Ramos, Cynthia; Müller, Ulrich

    2012-08-10

    During development of the mammalian cerebral cortex, radial glial cells (RGCs) generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which lower-layer neurons are formed before upper-layer neurons. It has been proposed that neuronal subtype fate is determined by birthdate through progressive restriction of the neurogenic potential of a common RGC progenitor. Here, we demonstrate that the murine cerebral cortex contains RGC sublineages with distinct fate potentials. Using in vivo genetic fate mapping and in vitro clonal analysis, we identified an RGC lineage that is intrinsically specified to generate only upper-layer neurons, independently of niche and birthdate. Because upper cortical layers were expanded during primate evolution, amplification of this RGC pool may have facilitated human brain evolution.

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

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    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.

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

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    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

    2012-02-15

    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 imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

  16. Serine racemase expression in mouse cerebral cortex after permanent focal cerebral ischemia

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    Li-zhen WANG; Xing-zu ZHU

    2004-01-01

    AIM: To study the alterations of the expressions of serine racemase in C57BL/6 mouse brain after permanent focal cerebral ischemia. METHODS: The mRNA level and the protein level of serine racemase were assayed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The amount of D-serine and L-serine were measured by HPLC. RESULTS: High levels of serine racemase were constitutively expressed in the normal cortex of mouse. At early stage after middle cerebral artery occlusion (MCAO), no significant change in expression of serine racemase was observed in temporoparietal cortex in ipsilateral hemisphere. However,delayed transient decreases of serine racemase in both mRNA and protein levels were detected from d 6 to d 10 after ischemia. Correspondingly, D-serine concentration also declined in the ipsilateral cortex during this period when compared with the D-serine level in the contralateral cortex. CONCLUSION:Delayed decreases in serine racemase expression and D-serine level occurred in the temporoparietal cortex at the late stage after focal cerebral ischemia.

  17. Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

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    Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

    2013-03-01

    We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

  18. A Synaptic Basis for Memory Storage in the Cerebral Cortex

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    Bear, Mark F.

    1996-11-01

    A cardinal feature of neurons in the cerebral cortex is stimulus selectivity, and experience-dependent shifts in selectivity are a common correlate of memory formation. We have used a theoretical ``learning rule,'' devised to account for experience-dependent shifts in neuronal selectivity, to guide experiments on the elementary mechanisms of synaptic plasticity in hippocampus and neocortex. These experiments reveal that many synapses in hippocampus and neocortex are bidirectionally modifiable, that the modifications persist long enough to contribute to long-term memory storage, and that key variables governing the sign of synaptic plasticity are the amount of NMDA receptor activation and the recent history of cortical activity.

  19. [Brodmann Areas 20, 21, and 22 in the Cerebral Cortex].

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    Kaga, Kimitaka; Minami, Shujiro B

    2017-04-01

    The 20, 21, and 22 areas in the temporal lobe as classified by Brodmann are almost identical with Economo and Koskinas's TA, TE1, and TE2, and, generally, with the gyrus, middle temporal gyrus, and inferior temporal gyrus according to brain anatomy. Before Brodmann's classification, Flechsig published his book "Soul and Brain" in 1897, in which primary, secondary, and association areas in the brain were classified. More recently, results from research using magnetic resonance imaging (MRI) and fMRI support the parcellation of the cerebral cortex proposed by Flechsig, Brodmann, and Economo more than one century ago.

  20. Functional involvement of cerebral cortex in human narcolepsy.

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    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.

  1. A multi-modal parcellation of human cerebral cortex.

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    Glasser, Matthew F; Coalson, Timothy S; Robinson, Emma C; Hacker, Carl D; Harwell, John; Yacoub, Essa; Ugurbil, Kamil; Andersson, Jesper; Beckmann, Christian F; Jenkinson, Mark; Smith, Stephen M; Van Essen, David C

    2016-08-11

    Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal 'fingerprint' of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.

  2. Biomaterial-engineering and neurobiological approaches for regenerating the injured cerebral cortex

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    Itsuki Ajioka

    2016-03-01

    Full Text Available The cerebral cortex is responsible for higher functions of the central nervous system (CNS, such as movement, sensation, and cognition. When the cerebral cortex is severely injured, these functions are irreversibly impaired. Although recent neurobiological studies reveal that the cortex has the potential for regeneration, therapies for functional recovery face some technological obstacles. Biomaterials have been used to evoke regenerative potential and promote regeneration in several tissues, including the CNS. This review presents a brief overview of new therapeutic strategies for cortical regeneration from the perspectives of neurobiology and biomaterial engineering, and discusses a promising technology for evoking the regenerative potential of the cerebral cortex.

  3. Tyrosine promotes oxidative stress in cerebral cortex of young rats.

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    Sgaravatti, Angela M; Vargas, Bethânia A; Zandoná, Bernardo R; Deckmann, Kátia B; Rockenbach, Francieli J; Moraes, Tarsila B; Monserrat, José M; Sgarbi, Mirian B; Pederzolli, Carolina D; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir; Dutra-Filho, Carlos Severo

    2008-10-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. In tyrosinemia type II, high levels of tyrosine are correlated with eyes, skin and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study, we investigated whether oxidative stress is elicited by l-tyrosine in cerebral cortex homogenates of 14-day-old Wistar rats. The in vitro effect of 0.1-4.0mM l-tyrosine was studied on the following oxidative stress parameters: total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), ascorbic acid content, reduced glutathione (GSH) content, spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), thiol-disulfide redox state (SH/SS ratio), protein carbonyl content, formation of DNA-protein cross-links, and the activities of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glucose-6-phosphate dehydrogenase (G6PDH). TRAP, TAR, ascorbic acid content, SH/SS ratio and CAT activity were significantly diminished, while formation of DNA-protein cross-link was significantly enhanced by l-tyrosine in vitro. In contrast, l-tyrosine did not affect the other parameters of oxidative stress evaluated. These results indicate that l-tyrosine decreases enzymatic and non-enzymatic antioxidant defenses, changes the redox state and stimulates DNA damage in cerebral cortex of young rats in vitro. This suggests that oxidative stress may represent a pathophysiological mechanism in tyrosinemic patients, in which this amino acid accumulates.

  4. Neuronal Polarity in the Embryonic Mammalian Cerebral Cortex

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    Elif Kon

    2017-06-01

    Full Text Available The cerebral cortex is composed of billions of neurons that can grossly be subdivided into two broad classes: inhibitory GABAergic interneurons and excitatory glutamatergic neurons. The majority of cortical neurons in mammals are the excitatory type and they are the main focus of this review article. Like many of the cells in multicellular organisms, fully differentiated neurons are both morphologically and functionally polarized. However, they go through several changes in polarity before reaching this final mature differentiated state. Neurons are derived from polarized neuronal progenitor/stem cells and their commitment to neuronal fate is decided by cellular and molecular asymmetry during their last division in the neurogenic zone. They migrate from their birthplace using so-called multipolar migration, during which they switch direction of movement several times, and repolarize for bipolar migration when the axon is specified. Therefore, neurons have to break their previous symmetry, change their morphology and adequately respond to polarizing signals during migration in order to reach the correct position in the cortex and start making connections. Finally, the dendritic tree is elaborated and the axon/dendrite morphological polarity is set. Here we will describe the function, establishment and maintenance of polarity during the different developmental steps starting from neural stem cell (NSC division, neuronal migration and axon specification at embryonic developmental stages.

  5. [Investigation of the Cerebral Cortex Using Magnetoencephalography(MEG)].

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    Kakigi, Ryusuke

    2015-04-01

    Cortical neurons are excited by signals from the thalamus that are conducted via thalamocortical fibers. As the cortex receives these signals, electric currents are conducted through the apical dendrites of pyramidal cells in the cerebral cortex. These electric currents generate magnetic fields. These electric and magnetic currents can be recorded by electroencephalography (EEG) and magnetoencephalography (MEG), respectively. The spatial resolution of MEG is higher than that of EEG because magnetic fields, unlike electric fields, are not affected by current conductivity. MEG also has several advantages over functional magnetic resonance imaging (fMRI). It (1) is completely non-invasive; (2) measures neuronal activity rather than blood flow or metabolic changes; (3) has a higher temporal resolution than fMRI on the order of milliseconds; (4) enables the measurement of stimulus-evoked and event-related responses; (5) enables the analysis of frequency (i.e., brain rhythm) response, which means that physiological changes can be analyzed spatiotemporally; and (6) enables the detailed analysis of results from an individual subject, which eliminates the need to average results over several subjects. This latter advantage of MEG therefore enables the analysis of inter-individual differences.

  6. Emerging roles of neural stem cells in cerebral cortex development and evolution.

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    Borrell, Víctor; Reillo, Isabel

    2012-07-01

    Expansion and folding of the cerebral cortex are landmark features of mammalian brain evolution, which are recapitulated during embryonic development. Neural stem cells and their derived germinal cells are coordinated during cerebral cortex development to produce the appropriate amounts and types of neurons. This process is further complicated in gyrencephalic species, where newborn neurons must disperse in the tangential axis to expand the cerebral cortex in surface area. Here, we review advances that have been made over the last decade in understanding the nature and diversity of telencephalic neural stem cells and their roles in cortical development, and we discuss recent progress on how newly identified types of cortical progenitor cell populations may have evolved to drive the expansion and folding of the mammalian cerebral cortex.

  7. Ethanol induces heterotopias in organotypic cultures of rat cerebral cortex.

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    Mooney, Sandra M; Siegenthaler, Julie A; Miller, Michael W

    2004-10-01

    Abnormalities in the migration of cortical neurons to ectopic sites can be caused by prenatal exposure to ethanol. In extreme cases, cells migrate past the pial surface and form suprapial heterotopias or 'warts'. We used organotypic slice cultures from 17-day-old rat fetuses to examine structural and molecular changes that accompany wart formation. Cultures were exposed to ethanol (0, 200, 400 or 800 mg/dl) and maintained for 2-32 h. Fixed slices were sectioned and immunolabeled with antibodies directed against calretinin, reelin, nestin, GFAP, doublecortin, MAP-2 and NeuN. Ethanol promoted the widespread infiltration of the marginal zone (MZ) with neurons and the focal formation of warts. The appearance of warts is time- and concentration-dependent. Heterotopias comprised migrating neurons and were not detected in control slices. Warts were associated with breaches in the array of Cajal-Retzius cells and with translocation of reelin-immunoexpression from the MZ to the outer limit of the wart. Ethanol also altered the morphology of the radial glia. Thus, damage to the integrity of superficial cortex allows neurons to infiltrate the MZ, and if the pial-subpial glial barrier is also compromised these ectopic neurons can move beyond the normal cerebral limit to form a wart.

  8. Microtubules in the Cerebral Cortex: Role in Memory and Consciousness

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    Woolf, Nancy J.

    This chapter raises the question whether synaptic connections in the cerebral cortex are adequate in accounting for higher cognition, especially cognition involving multimodal processing. A recent and novel approach to brain mechanics is outlined, one that involves microtubules and microtubule-associated protein-2 (MAP2). In addition to effects on the neuronal membrane, neurotransmitters exert actions on microtubules. These neurotransmitter effects alter the MAP2 phosphorylation state and rates of microtubule polymerization and transport. It is argued that these processes are important to the physical basis of memory and consciousness. In support of this argument, MAP2 is degraded with learning in discrete cortical modules. How this relates to synaptic change related to learning is unknown. The specific proposal is advanced that learning alters microtubules in the subsynaptic zone lying beneath the synapse, and that this forms the physical basis of long-term memory storage because microtubule networks determine the synapse strength by directing contacts with actin filaments and transport of synaptic proteins. It is argued that this is more probable than memory-related physical storage in the synapse itself. Comparisons to consciousness are made and it is concluded that there is a link between microtubules, memory and consciousness.

  9. Neural field theory of plasticity in the cerebral cortex.

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    Fung, P K; Haber, A L; Robinson, P A

    2013-02-07

    A generalized timing-dependent plasticity rule is incorporated into a recent neural field theory to explore synaptic plasticity in the cerebral cortex, with both excitatory and inhibitory populations included. Analysis in the time and frequency domains reveals that cortical network behavior gives rise to a saddle-node bifurcation and resonant frequencies, including a gamma-band resonance. These system resonances constrain cortical synaptic dynamics and divide it into four classes, which depend on the type of synaptic plasticity window. Depending on the dynamical class, synaptic strengths can either have a stable fixed point, or can diverge in the absence of a separate saturation mechanism. Parameter exploration shows that time-asymmetric plasticity windows, which are signatures of spike-timing dependent plasticity, enable the richest variety of synaptic dynamics to occur. In particular, we predict a zone in parameter space which may allow brains to attain the marginal stability phenomena observed experimentally, although additional regulatory mechanisms may be required to maintain these parameters.

  10. Radial glial dependent and independent dynamics of interneuronal migration in the developing cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Yukako Yokota

    Full Text Available Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex.

  11. 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.

  12. BrdU-labelled neurons regeneration after cerebral cortex injury in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yue-lin; QIU Shu-dong; ZHANG Peng-bo; SHI Wei

    2006-01-01

    @@ Mechanical injuries to the external regions of the brain including the cerebral cortex and other parts of the telencephalon are common yet relatively untreatable.1 The predicament in recovery from brain injury is that the adult central nervous system is generally thought to be incapable of replacing dead neurons. As the subventricular zone (SVZ) is now known to be neurogenic and is in close proximity to the cerebral cortex and other functionally important forebrain areas, the neurogeny of SVZ brings hope to the repair of brain injury.2,3 Because of the high frequency of injuries to the cerebral cortex and its functional importance in humans, many laboratories have studied the results of unilateral aspiration or percussion injury of the cerebral cortex.4-6 However,little is known about the response of endogenous neural stem/progenitor cells following loss of the cerebral cortex that commonly occurred in the neurosurgery. We have characterized the time course of the proliferation of neural stem/progenitor cells in the SVZ in brain to loss of cortical cells.

  13. Coenzyme q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex.

    Science.gov (United States)

    Majumdar, Anuradha S; Nirwane, Abhijit; Kamble, Rahul

    2014-05-01

    The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.

  14. Amygdala kindling potentiates seizure-stimulated immediate-early gene expression in rat cerebral cortex.

    Science.gov (United States)

    Duman, R S; Craig, J S; Winston, S M; Deutch, A Y; Hernandez, T D

    1992-11-01

    Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute electroconvulsive seizure (ECS). Although amygdala kindling did not significantly influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in the cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was dependent on the time course of kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased in stage 2 kindled animals. ECS-stimulated levels of c-jun and NGF1-A mRNA were also significantly increased in cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was long-lasting because an acute ECS stimulus significantly elevated levels of c-fos and c-jun mRNA in the cerebral cortex of animals that were kindled 5 months previously. In contrast to these effects in cerebral cortex, kindling did not influence ECS-stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical studies revealed lamina-specific changes in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Mark R. Winter

    2015-10-01

    Full Text Available Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex.

  16. 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.

  17. THE EFFECT OF LIGUSTRAZINE ON NEUROGENESIS IN CORTEX AFTER FOCAL CEREBRAL ISCHEMIA IN RATS

    Institute of Scientific and Technical Information of China (English)

    Qiu Fen; Liu Yong; Zhang Pengbo; Kang Qianyan; Tian Yingfang; Chen Xinlin; Zhao Jianjun; Qi Cunfang

    2006-01-01

    Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral arteryocclusion with asuture. Two hours later, injection of Ligustrazine (80 mg/kg, 1 time/d) was performed peritoneally. Four hours after the ischemia,5-bromodeoxyuridine (BrdU) (50 mg/kg, 1 time/d) was injected peritoneally. At 7 d, 14 d and 21 d after ischemia,BrdU positive cells in the cortex were observed by immunohistochemical staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ - Ⅵ layers of the ipsilateral cortex, with a band-like distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased.In Ligustrazine group, BrdU positive cells were also observed in the Ⅱ - Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7 d, 14 d and 21 d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.

  18. Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

    DEFF Research Database (Denmark)

    Dreier, Jens P; Major, Sebastian; Pannek, Heinz-Wolfgang

    2012-01-01

    Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating...

  19. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  20. RTTN mutations link primary cilia function to organization of the human cerebral cortex

    NARCIS (Netherlands)

    S.K. Kia; E. Verbeek (Elly); M.P. Engelen (Erik); R. Schot (Rachel); R.A. Poot (Raymond); I.F.M. de Coo (René); M. Leguin (Maarten); C.J. Poulton (Cathryn); F. Pourfarzad, F. (Farzin); F.G. Grosveld (Frank); A. Brehm (António); M.C.Y. de Wit (Marie Claire); R. Oegema (Renske); W.B. Dobyns (William); F.W. Verheijen (Frans); G.M.S. Mancini (Grazia)

    2012-01-01

    textabstractPolymicrogyria is a malformation of the developing cerebral cortex caused by abnormal organization and characterized by many small gyri and fusion of the outer molecular layer. We have identified autosomal-recessive mutations in RTTN, encoding Rotatin, in individuals with bilateral diffu

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

    NARCIS (Netherlands)

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

    1993-01-01

    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

  2. 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 ac...

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Eleni-Maria Amaniti

    Full Text Available 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.

  6. [Histostructural changes of rat cerebral cortex during hemorrhagic stroke modeling].

    Science.gov (United States)

    Savos'ko, S I; Chaĭkovs'kyĭ, Iu B; Pogoriela, N Kh; Makarenko, O M

    2012-01-01

    Pathological changes during modeling of primary and secondary acute hemorrhagic stroke were studied in rats. We revealed differences in the activity of pharmacological action of medications under condition of acute stroke. The action of medications increased viability of neurons in both hemispheres of rat cerebrum at a right-side primary and secondary hemorrhagic stroke. Following secondary stroke, the amount of degenerative neurons amounted 25.5 +/- 0.8 cells/mm2, following the action ofcerebrolysin this value was 17.6 +/- 1.7 cells/ mm2 and after the action of cortexine and cerebral this value amounted 18.0 +/- 0.9 cells/mm2 and 10.7 +/- 0.4 cells/ mm2, respectively. In control animals the number of degenerative neurons did not exceed 2% and averaged 1.5 +/- 0.1 cells/mm2. Analysis of the morphological and statistical data showed that the most effective remedies under the primary and secondary hemorrhagic insult are cortexine and cerebral. Cerebral was found to be more effective.

  7. 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.

  8. Reduced Numbers of Somatostatin Receptors in the Cerebral Cortex in Alzheimer's Disease

    Science.gov (United States)

    Flint Beal, M.; Mazurek, Michael F.; Tran, Vinh T.; Chattha, Geetinder; Bird, Edward D.; Martin, Joseph B.

    1985-07-01

    Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatinlike immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

  9. 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.

  10. Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates

    Directory of Open Access Journals (Sweden)

    Xue-mei Zhang

    2009-10-01

    Full Text Available A novel population of cells that express typical immature neuronal markers including doublecortin (DCX+ has been recently identified throughout the adult cerebral cortex of relatively large mammals (guinea pig, rabbit, cat, monkey and human. These cells are more common in the associative relative to primary cortical areas and appear to develop into interneurons including type II nitrinergic neurons. Here we further describe these cells in the cerebral cortex and amygdala, in comparison with DCX+ cells in the hippocampal dentate gyrus, in 3 age groups of rhesus monkeys: young adult (12.3±0.2 yrs, n=3, mid-age (21.2±1.9 yrs, n=3 and aged (31.3±1.8 yrs, n=4. DCX+ cells with a heterogeneous morphology persisted in layers II/III primarily over the associative cortex and amygdala in all groups (including in two old animals with cerebral amyloid pathology, showing a parallel decline in cell density with age across regions. In contrast to the cortex and amygdala, DCX+ cells in the subgranular zone diminished in the mid-age and aged groups. DCX+ cortical cells might arrange as long tangential migratory chains in the mid-age and aged animals, with apparently distorted cell clusters seen in the aged group. Cortical DCX+ cells colocalized commonly with polysialylated neural cell adhesion molecule (PSA-NCAM and partially with neuron-specific nuclear protein (NeuN and γ-aminobutyric acid (GABA, suggesting a potential differentiation of these cells into interneuron phenotype. These data suggest a life-long role for immature interneuron-like cells in the associative cerebral cortex and amygdala in nonhuman primates.

  11. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  12. Visual motion discrimination by propagating patterns in primate cerebral cortex.

    Science.gov (United States)

    Townsend, Rory; Solomon, Selina S; Martin, Paul R; Solomon, Samuel G; Gong, Pulin

    2017-09-14

    Visual stimuli can evoke waves of neural activity that propagate across the surface of visual cortical areas. The relevance of these waves for visual processing is unknown. Here we measured the phase and amplitude of local field potentials (LFPs) in electrode array recordings from motion-processing medial temporal area (MT) of anesthetized male marmosets. Animals viewed grating or dot-field stimuli drifting in different directions. We found that on individual trials, the direction of LFP wave propagation is sensitive to the direction of stimulus motion. Propagating LFP patterns are also detectable in trial-averaged activity, but the trial-averaged patterns exhibit different dynamics and behaviors to those in single trials and are similar across motion directions. We show that this difference arises because stimulus-sensitive propagating patterns are present in the phase of single-trial oscillations, whereas the trial-averaged signal is dominated by additive amplitude effects. Our results demonstrate that propagating LFP patterns can represent sensory inputs, at timescales relevant to visually-guided behaviors, and raise the possibility that propagating activity patterns serve neural information processing in area MT and other cortical areas.SIGNIFICANCE STATEMENTPropagating wave patterns are widely observed in the cortex, but their functional relevance remains unknown. We show here that visual stimuli generate propagating wave patterns in local field potentials (LFPs) in a movement-sensitive area of the primate cortex, and that the propagation direction of these patterns is sensitive to stimulus motion direction. We also show that averaging LFP signals across multiple stimulus presentations (trial-averaging) yields propagating patterns which capture different dynamic properties of the LFP response and show negligible direction sensitivity. Our results demonstrate that sensory stimuli can reliably modulate propagating wave patterns in the cortex. The relevant

  13. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  14. Amino acid incorporation into the protein of mitochondrial preparations from cerebral cortex and spinal cord.

    Science.gov (United States)

    Bachelard, H S

    1966-07-01

    1. Washed guinea-pig cerebral-cortex mitochondria incorporate [(14)C]leucine into their protein at a rate comparable with the rates reported for liver or heart mitochondria only if the mitochondria are separated from myelin and nerve endings by density-gradient centrifugation. 2. The non-mitochondrial components (myelin and nerve endings) of brain mitochondrial preparations incorporated [(14)C]leucine at a negligible rate. 3. The mitochondria do not require an exogenous supply of energy or a full supply of amino acids to support the process. 4. The incorporation rate was linear up to 2hr. aerobic incubation at 30 degrees and was inhibited by chloramphenicol, only slightly by actinomycin D and not by penicillin or pretreatment with ribonuclease. The observed incorporation is considered to be unlikely to be due to contaminating cytoplasmic ribosomes or bacteria. 5. The process was also studied in mitochondrial preparations from rabbit cerebral cortex and spinal cord.

  15. Small scale module of the rat granular retrosplenial cortex: an example of minicolumn-like structure of the cerebral cortex

    Directory of Open Access Journals (Sweden)

    Noritaka eIchinohe

    2012-01-01

    Full Text Available Structures associated with the small scale module called minicolumn can be observed frequently in the cerebral cortex. However, the description of functional characteristics remains obscure. A significant confounding factor is the marked variability both in the definition of a minicolumn and in the diagnostic markers for identifying a minicolumn (see for review, Jones, 2000, DeFelipe et al., 2003; Rockland and Ichinohe, 2004. Within a minicolumn, cell columns are easily visualized by conventional Nissl staining. Dendritic bundles were first discovered with Golgi methods, but are more easily seen with MAP2-immunohistochemisty. Myelinated axon bundles can be seen by Tau-immunohistochemistry or myelin staining. Axon bundles of double bouquet cell can be seen by calbindin-immunohistochemistry. The spatial interrelationship among these morphological elements is more complex than expected and is neither clear nor unanimously agreed upon. In this review, I would like to focus first on the minicolumnar structure found in layers 1 and 2 of the rat granular retrosplenial cortex (GRS. This modular structure was first discovered as a combination of prominent apical dendritic bundles from layer 2 pyramidal neurons and spatially-matched thalamocortical patchy inputs (Wyss et al., 2000. Further examination showed more intricate components of this modular structure, which will be reviewed in this paper. Second, the postnatal development of this structure and potential molecular players for its formation will be reviewed. Thirdly, I will discuss how this modular organization is transformed in mutant rodents with a disorganized layer structure in the cerebral cortex (i.e., reeler mouse and Shaking Rat Kawasaki. Lastly, the potential significance of this type of module will be discussed.

  16. Decreased light attenuation in cerebral cortex during cerebral edema detected using optical coherence tomography

    OpenAIRE

    Rodriguez, Carissa L. R.; Szu, Jenny I.; Eberle, Melissa M.; Wang, Yan; Hsu, Mike S.; Binder, Devin K.; Park, B. Hyle

    2014-01-01

    Abstract. Cerebral edema develops in response to a variety of conditions, including traumatic brain injury and stroke, and contributes to the poor prognosis associated with these injuries. This study examines the use of optical coherence tomography (OCT) for detecting cerebral edema in vivo. Three-dimensional imaging of an in vivo water intoxication model in mice was performed using a spectral-domain OCT system centered at 1300 nm. The change in attenuation coefficient was calculated and cere...

  17. Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats

    OpenAIRE

    Şenol, Nilgün; Nazıroğlu, Mustafa

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We investigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, a...

  18. Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

    OpenAIRE

    Sansom, Stephen N; Frederick J Livesey

    2009-01-01

    In the developing brain, gradients are commonly used to divide neurogenic regions into distinct functional domains. In this article, we discuss the functions of morphogen and gene expression gradients in the assembly of the nervous system in the context of the development of the cerebral cortex. The cerebral cortex is a mammal-specific region of the forebrain that functions at the top of the neural hierarchy to process and interpret sensory information, plan and organize tasks, and to control...

  19. Glycine intracerebroventricular administration disrupts mitochondrial energy homeostasis in cerebral cortex and striatum of young rats.

    Science.gov (United States)

    Moura, Alana Pimentel; Grings, Mateus; Dos Santos Parmeggiani, Belisa; Marcowich, Gustavo Flora; Tonin, Anelise Miotti; Viegas, Carolina Maso; Zanatta, Angela; Ribeiro, César Augusto João; Wajner, Moacir; Leipnitz, Guilhian

    2013-11-01

    High tissue levels of glycine (GLY) are the biochemical hallmark of nonketotic hyperglycinemia (NKH), an inherited metabolic disease clinically characterized by severe neurological symptoms and brain abnormalities. Considering that the mechanisms underlying the neuropathology of this disease are not fully established, the present work investigated the in vivo effects of intracerebroventricular administration of GLY on important parameters of energy metabolism in cerebral cortex and striatum from young rats. Our results show that GLY reduced CO₂ production using glucose as substrate and inhibited the activities of citrate synthase and isocitrate dehydrogenase in striatum, whereas no alterations of these parameters were verified in cerebral cortex 30 min after GLY injection. We also observed that GLY diminished the activities of complex IV in cerebral cortex and complex I-III in striatum at 30 min and inhibited complex I-III activity in striatum at 24 h after its injection. Furthermore, GLY reduced the activity of total and mitochondrial creatine kinase in both brain structures 30 min and 24 h after its administration. In contrast, the activity of Na⁺, K⁺-ATPase was not altered by GLY. Finally, the antioxidants N-acetylcysteine and creatine, and the NMDA receptor antagonist MK-801 attenuated or fully prevented the inhibitory effects of GLY on creatine kinase and respiratory complexes in cerebral cortex and striatum. Our data indicate that crucial pathways for energy production and intracellular energy transfer are severely compromised by GLY. It is proposed that bioenergetic impairment induced by GLY in vivo may contribute to the neurological dysfunction found in patients affected by NKH.

  20. 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.

  1. Early milk availability modulates the activity of choline acetyltransferase in the cerebral cortex of rats.

    Science.gov (United States)

    Aizawa, Shu; Nakamura, Ryosuke; Yamaguchi, Yuki; Sensui, Naoto; Yamamuro, Yutaka

    2011-10-01

    The purpose of the present study was to investigate the effect of milk in the early stage of lactation on the maturation of cholinergic neurons in the cerebral cortex of rats. Pups were removed from their mothers immediately following parturition and placed with foster dams at days 5-7 of lactation. At days 18 and 56 after birth, the activity of choline acetyltransferase (ChAT), an enzyme responsible for acetylcholine synthesis, in different areas of the cerebral cortex was examined by high-performance liquid chromatography electrochemical detection. In the frontal and hindlimb/parietal regions of the cerebral cortex, the lack of early milk significantly decreased ChAT activity at days 18 and 56. There was no effect on gains in the body or brain weight of infants. ChAT activity in the occipital area tended to be lower in the early milk-deprived rats. The intake of early milk potentially contributes not only to nutrients for the growth of newborn infants, but also to the functional maturation of the cholinergic neurotransmission system in a region-specific manner.

  2. 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.

  3. Culture and Identification of Monoclonal Neural Stem Cells Derived from Cerebral Cortex

    Institute of Scientific and Technical Information of China (English)

    TAO Kaixiong; CHEN Jingbo; WANG Guobin; SHU Xiaogang

    2006-01-01

    To isolate and culture the purified monoclonal neural stem cells from the cerebral cortex of new born mice, new-born mice cerebral cortex was isolated and dissociated to single-cell suspension by mechanical trituration. The dissociated single cells were cultured in serum-free medium. After the formation of neurospheres, single-cell clone culture was performed by limiting dilution and the proliferated single-cell clones were harvested for subculture. Immunocytochemistry was used to detect the specific marker of neuroepithelial stem cells (Nestin) of the primary and monoclonal neurospheres. In the differentiated cells we detected the specific antigen of NF-200 and GFAP. Our results showed that the primary neurospheres expressed Nestin antigen positively. By limiting dilution, we cultured the cell lines from single-cell clone and the monoclonal neurospheres expressed Nestin and had capabilities of self-renewal, proliferation and the potentiality of differentiation into neurons and glial cells. It is concluded that monoclonal neural stem cells which have the ability of proliferation and multi-directional differentiation can be isolated and cultured from the cerebral cortex of new-born mice by limiting dilution.

  4. Mouse embryos and chimera cloned from neural cells in the postnatal cerebral cortex.

    Science.gov (United States)

    Makino, Hatsune; Yamazaki, Yukiko; Hirabayashi, Takahiro; Kaneko, Ryosuke; Hamada, Shun; Kawamura, Yoshimi; Osada, Tomoharu; Yanagimachi, Ryuzo; Yagi, Takeshi

    2005-01-01

    Cloning of mice has been achieved by transferring nuclei of various types of somatic cell nuclei into enucleated oocytes. However, all attempts to produce live cloned offspring using the nuclei of neurons from adult cerebral cortex have failed. Previously we obtained cloned mice using the nuclei of neural cells collected from fetal cerebral cortex. Here, we attempted to generate cloned mice using differentiated neurons from the cerebral cortex of postnatal (day 0-4) mice. Although we were unable to obtain live cloned pups, many fetuses reached day 10.5 days of development. These fetuses showed various abnormalities such as spherical omission of the neuroepithelium, collapsed lumen of neural tube, and aberrant expressions of marker proteins of neurons. We produced chimeric mice in which some hair cells and kidney cells were originated from differentiated neurons. In chimeric fetuses, LacZ-positive donor cells were in all three germ cell layers. However, chimeras with large contribution of donor-derived cells were not obtained. These results indicate that nuclei of differentiated neurons have lost their developmental totipotency. In other words, the conventional nuclear transfer technique does not allow nuclei of differentiated neurons to undergo complete genomic reprogramming required for normal embryonic development.

  5. Structural and functional analyses of human cerebral cortex using a surface-based atlas

    Science.gov (United States)

    Van Essen, D. C.; Drury, H. A.

    1997-01-01

    We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

  6. The cerebral cortex of the pygmy hippopotamus, Hexaprotodon liberiensis (Cetartiodactyla, Hippopotamidae): MRI, cytoarchitecture, and neuronal morphology.

    Science.gov (United States)

    Butti, Camilla; Ewan Fordyce, R; Ann Raghanti, Mary; Gu, Xiaosi; Bonar, Christopher J; Wicinski, Bridget A; Wong, Edmund W; Roman, Jessica; Brake, Alanna; Eaves, Emily; Spocter, Muhammad A; Tang, Cheuk Y; Jacobs, Bob; Sherwood, Chet C; Hof, Patrick R

    2014-04-01

    The structure of the hippopotamus brain is virtually unknown because few studies have examined more than its external morphology. In view of their semiaquatic lifestyle and phylogenetic relatedness to cetaceans, the brain of hippopotamuses represents a unique opportunity for better understanding the selective pressures that have shaped the organization of the brain during the evolutionary process of adaptation to an aquatic environment. Here we examined the histology of the cerebral cortex of the pygmy hippopotamus (Hexaprotodon liberiensis) by means of Nissl, Golgi, and calretinin (CR) immunostaining, and provide a magnetic resonance imaging (MRI) structural and volumetric dataset of the anatomy of its brain. We calculated the corpus callosum area/brain mass ratio (CCA/BM), the gyrencephalic index (GI), the cerebellar quotient (CQ), and the cerebellar index (CI). Results indicate that the cortex of H. liberiensis shares one feature exclusively with cetaceans (the lack of layer IV across the entire cerebral cortex), other features exclusively with artiodactyls (e.g., the morphologiy of CR-immunoreactive multipolar neurons in deep cortical layers, gyrencephalic index values, hippocampus and cerebellum volumetrics), and others with at least some species of cetartiodactyls (e.g., the presence of a thick layer I, the pattern of distribution of CR-immunoreactive neurons, the presence of von Economo neurons, clustering of layer II in the occipital cortex). The present study thus provides a comprehensive dataset of the neuroanatomy of H. liberiensis that sets the ground for future comparative studies including the larger Hippopotamus amphibius. Copyright © 2014 Wiley Periodicals, Inc.

  7. Effect of Electroacupuncture on Expression of p53 Protein in Cerebral Cortex of Rats with Global Cerebral Ischemia/Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 葛巍; 徐兴顺; 曾因明

    2004-01-01

    Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism. Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded.To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint "Zusanli"(ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method. Results: Cells with positive p53 immunoreactivity in the cerebral cortex of rats in the IR group was significantly higher than that in the control group ( P<0.05), while that in the IR-EA group was significantly lower than that in the IR group (P<0.05). Conclusion: EA could remarkably reduce expression of p53 protein in the cerebral cortex of senile rats with global cerebral IR injury, which might be one of the means for EA to inhibit neuronal apoptosis after cerebral IR injury.

  8. 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.

  9. Pine pollen inhibits cell apoptosis-related protein expression in the cerebral cortex of mice with arsenic poisoning

    Institute of Scientific and Technical Information of China (English)

    Yanhong Luo; Yaodong Wei; Taizhong Wang; Dongzhu Chen; Tiansheng Lu; Ruibo Wu; Keke Si

    2012-01-01

    Previous studies have demonstrated that pine pollen can inhibit cerebral cortical cell apoptosis in mice with arsenic poisoning. The present study sought to detect the influence of pine pollen on apoptosis-related proteins. Immunohistochemistry, western blotting and enzyme-linked immuno-sorbent assays were used to measure the levels of apoptosis-related proteins in the cerebral cortex of mice with arsenic poisoning. Results indicated that pine pollen suppressed cell apoptosis in the cerebral cortex of arsenic-poisoned mice by reducing Bax, Bcl-2 protein expression and increasing p53 protein expression.

  10. (/sup 3/H)pirenzepine selectively identifies a high affinity population of muscarinic cholinergic receptors in the rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Watson, M.; Roeske, W.R.; Yamamura, H.I.

    1982-11-01

    The specific binding of (/sup 3/H)pirenzepine was investigated in homogenates of rat cerebral cortex, cerebellar cortex, and heart. Specific binding of (/sup 3/H)pirenzepine in the cerebral cortex as defined by displacement with atropine sulfate (1..mu..M) was of high affinity (K/sub d/ = 4-10 nM, receptor density = 1.06 pmoles/mg protein), stereoselective, and competitive with drugs specific for the muscarinic receptor. In contrast, few (/sup 3/H)pirenzepine binding sites were demonstrated in cerebellar and heart homogenates.

  11. 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.

  12. 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.

  13. Enhanced metabolic capacity of the frontal cerebral cortex after Pavlovian conditioning.

    Science.gov (United States)

    Bruchey, A K; Gonzalez-Lima, F

    2008-03-18

    While Pavlovian conditioning alters stimulus-evoked metabolic activity in the cerebral cortex, less is known about the effects of Pavlovian conditioning on neuronal metabolic capacity. Pavlovian conditioning may increase prefrontal cortical metabolic capacity, as suggested by evidence of changes in cortical synaptic strengths, and evidence for a shift in memory initially processed in subcortical regions to more distributed prefrontal cortical circuits. Quantitative cytochrome oxidase histochemistry was used to measure cumulative changes in brain metabolic capacity associated with both cued and contextual Pavlovian conditioning in rats. The cued conditioned group received tone-foot-shock pairings to elicit a conditioned freezing response to the tone conditioned stimulus, while the contextually conditioned group received pseudorandom tone-foot-shock pairings in an excitatory context. Untrained control group was handled daily, but did not receive any tone presentations or foot shocks. The cued conditioned group had higher cytochrome oxidase activity in the infralimbic and anterior cingulate cortex, and lower cytochrome oxidase activity in dorsal hippocampus than the other two groups. A significant increase in cytochrome oxidase activity was found in anterior cortical areas (medial, dorsal and lateral frontal cortex; agranular insular cortex; lateral and medial orbital cortex and prelimbic cortex) in both conditioned groups, as compared with the untrained control group. In addition, no differences in cytochrome oxidase activity in the somatosensory regions and the amygdala were detected among all groups. The findings indicate that cued and contextual Pavlovian conditioning induces sustained increases in frontal cortical neuronal metabolic demand resulting in regional enhancement in the metabolic capacity of anterior cortical regions. Enhanced metabolic capacity of these anterior cortical areas after Pavlovian conditioning suggests that the frontal cortex may play a

  14. 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.

  15. 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

  16. Role of cerebral cortex in the neuropathology of Huntington´s disease

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    Ana María Estrada-Sánchez

    2013-02-01

    Full Text Available An expansion of glutamine repeats in the N-terminal domain of the huntingtin protein leads to Huntington´s disease (HD, a neurodegenerative condition characterized by the presence of involuntary movements, dementia, and psychiatric disturbances. Evaluation of postmortem HD tissue indicates that the most prominent cell loss occurs in cerebral cortex and striatum, forebrain regions in which cortical pyramidal neurons (CPNs and striatal medium spiny neurons (MSNs are the most affected. Subsequent evidence obtained from HD patients and especially from transgenic mouse models of HD indicates that long before neuronal death, patterns of communication between CPNs and MSNs become dysfunctional. In fact, electrophysiological signaling in transgenic HD mice is altered even before the appearance of the HD behavioral phenotype, suggesting that dysfunctional cortical input to the striatum sets the stage for the emergence of HD neurological signs. Striatal MSNs, moreover, project back to cortex via multi-synaptic connections, allowing for even further disruptions in cortical processing. An effective therapeutic strategy for HD, therefore, may lie in understanding the synaptic mechanisms by which it dysregulates the corticostriatal system. Here, we review literature evaluating the molecular, morphological, and physiological alterations in the cerebral cortex, a key component of brain circuitry controlling motor behavior, as they occur in both patients and transgenic HD models.

  17. Analysis of Presenilin 1 and 2 interacting proteins in mouse cerebral cortex during development.

    Science.gov (United States)

    Kumar, Ashish; Thakur, M K

    2014-11-01

    In our previous report, we showed that Presenilin (PS)1 and 2 have differential expression profile from early embryonic stages till adulthood in mouse cerebral cortex, suggesting that both of these proteins are crucial for brain development. Genetic manipulation studies have also shown the involvement of PS1 in brain development, but PS2 remains largely unexplored. In order to understand how PS1 and 2 mediate developmental functions, we have investigated the interaction of PS1 and 2 with proteins of mouse cerebral cortex during development. Co-immunoprecipitation (Co-IP) combined with MALDI-MS/MS analysis revealed 12 interacting partners of PS1 and 11 partners of PS2. The interacting proteins were different for PS1 and 2, and involved in cell division, glycolysis, cell adhesion and protein trafficking. Densitometric analysis of protein bands visualized after SDS-PAGE separation of Co-IP proteins revealed variation in their amount and degree of interaction during different developmental stages of mice. Further, immunoblot based validation of PS1 interacting protein Notch-1 showed maximum interaction at embryonic day (E) 12.5, decline at E18.5, upregulation from postnatal day 0 (P0) to P20 and thereafter reduction at P45 and 20 weeks. In-silico analysis of PS and its interacting proteins indicated conformation based interaction through common type of secondary structures having alpha helical, extended beta strand and random coil, and CK2, PKC phosphorylation and myristoylation motifs. Taken together, our study showed that PS1 and PS2 interact to varying extent with different proteins of mouse cerebral cortex and suggests their interaction based on specific conformation and involvement in diverse functions essential for the brain development.

  18. [Effect of nootropic agents on impulse activity of cerebral cortex neurons].

    Science.gov (United States)

    Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

    2001-01-01

    The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

  19. 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.

  20. 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.

  1. Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

    Institute of Scientific and Technical Information of China (English)

    Nilgnenol; Mustafa Nazrolu

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

  2. Effect of Magnesium on Nitric Oxide Synthase of Neurons in Cortex during Early Period of Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    SUN Xiu; MEI Yuanwu; TONG E'tang

    2000-01-01

    To investigate the effect of magnesium on nitric oxide synthase (NOS) of neurons in cortex during early cerebral ischemic period, a rat model of middle cerebral artery occlusion (MCAO) was established. The results showed that the NOS activity of neurons in cortex was increased significantly at 15 min after MCAO, reached its peak at 30 min after MCAO and returned to normal levels at 60 min after MCAO. The NOS activity of neurons in the magnesium-treated group was decreased significantly as compared with that in the ischemic group at 15 min and 30min after MCAO respectively. The results suggested that magnesium could inhibit the elevated NOS activity of neurons in cortex induced by cerebral ischemia.

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

    Science.gov (United States)

    Seibert, Tyler M; Karunamuni, Roshan; Kaifi, Samar; Burkeen, Jeffrey; Connor, Michael; Krishnan, Anitha Priya; White, Nathan S; Farid, Nikdokht; Bartsch, Hauke; Murzin, Vyacheslav; Nguyen, Tanya T; Moiseenko, Vitali; Brewer, James B; McDonald, Carrie R; Dale, Anders M; Hattangadi-Gluth, Jona A

    2017-04-01

    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. 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. 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). Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of

  4. 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.

  5. 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

  6. 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.

  7. Astrocytic response in hippocampus and cerebral cortex in an experimental epilepsy model.

    Science.gov (United States)

    Girardi, Elena; Ramos, Alberto Javier; Vanore, Gabriela; Brusco, Alicia

    2004-02-01

    Astrocytes are very sensitive to alterations in the brain environment and respond showing a phenomenon known as astroglial reaction. S100beta is an astroglial derived neurotrophic factor, seems to be involved in neuroplasticity. The aim of this work was to study the astrocytic response in rat hippocampus and cerebral cortex after repetitive seizures induced by 3-mercaptopropionic acid (MP) administration. Immunocytochemical studies were performed to analyze GFAP and S100beta expression. Both studied areas showed hypertrophied astrocytes with enlarged processes and increased soma size. Astrocyte hyperplasia was observed only in the cerebral cortex. A significant decrease in the astrocytic S100beta immunostaining occurs after MP treatment. These results indicate that MP administration induces an astroglial reaction with reduced intracellular S100beta level. The observed reduction in astroglial S100beta could be related to the release of this factor to the extracellular space, where it may produce neurotrophic or deleterious effects accordingly to the concentration achieved. The mechanism of this remains to be elucidated.

  8. Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex.

    Science.gov (United States)

    Sgaravatti, Angela M; Magnusson, Alessandra S; de Oliveira, Amanda S; Rosa, Andréa P; Mescka, Caroline Paula; Zanin, Fernanda R; Pederzolli, Carolina D; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir; Dutra-Filho, Carlos Severo

    2009-09-01

    Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism especially in tyrosinemia type II which is caused by deficiency of tyrosine aminotransferase (TAT) and provokes eyes, skin and central nervous system disturbances. We have recently reported that tyrosine promoted oxidative stress in vitro but the exact mechanisms of brain damage in these disorder are poorly known. In the present study, we investigated the in vivo effect of L-tyrosine (500 mg/Kg) on oxidative stress indices in cerebral cortex homogenates of 14-day-old Wistar rats. A single injection of L-tyrosine decreased glutathione (GSH) and thiol-disulfide redox state (SH/SS ratio) while thiobarbituric acid-reactive substances, protein carbonyl content and glucose-6-phosphate dehydrogenase activity were enhanced. In contrast, the treatment did not affect ascorbic acid content, and the activities of superoxide dismutase, catalase and glutathione peroxidase. These results indicate that acute administration of L-tyrosine may impair antioxidant defenses and stimulate oxidative damage to lipids and proteins in cerebral cortex of young rats in vivo. This suggests that oxidative stress may represent a pathophysiological mechanism in hypetyrosinemic patients.

  9. Noradrenalin and dopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex

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    Shinobu eNomura

    2014-08-01

    Full Text Available Noradrenergic fibers innervate the entire cerebral cortex, whereas the cortical distribution ofdopaminergic fibers is more restricted. However, the relative functional impact ofnoradrenalin and dopamine receptors in various cortical regions is largely unknown. Using aspecific genetic label, we first confirmed that noradrenergic fibers innervate the entire cortexwhereas dopaminergic fibers were present in all layers of restricted medial and lateral areasbut only in deep layers of other areas. Imaging of a genetically-encoded sensor revealed thatnoradrenalin and dopamine widely activate PKA in cortical pyramidal neurons of frontal,parietal and occipital regions with scarce dopaminergic fibers. Responses to noradrenalin hadhigher amplitude, velocity and occurred at more than 10 fold lower dose than those elicited bydopamine, whose amplitude and velocity increased along the antero-posterior axis. Thepharmacology of these responses was consistent with the involvement of Gs-coupled beta1adrenergic and D1/D5 dopaminergic receptors, but the inhibition of both noradrenalin anddopamine responses by beta adrenergic antagonists was suggestive of the existence of beta1-D1/D5 heteromeric receptors. Responses also involved Gi-coupled alpha2 adrenergic and D2-like dopaminergic receptors that markedly reduced their amplitude and velocity andcontributed to their cell-to-cell heterogeneity. Our results reveal that noradrenalin anddopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex withmoderate regional and laminar differences. These receptors can thus mediate widespreadeffects of both catecholamines, which are reportedly co-released by cortical noradrenergicfibers beyond the territory of dopaminergic fibers.

  10. Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro.

    Science.gov (United States)

    da Silva, Cleide G; Bueno, Ana Rúbia F; Schuck, Patrícia F; Leipnitz, Guilhian; Ribeiro, César A J; Rosa, Rafael B; Dutra Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir

    2004-01-01

    D-2-Hydroxyglutaric acid (DGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as D-2-hydroxyglutaric aciduria (DHGA). Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of DGA on total, cytosolic, and mitochondrial creatine kinase (CK) activities from cerebral cortex of 30-day-old Wistar rats. Total CK activity (tCK) was measured in whole cell homogenates, whereas cytosolic and mitochondrial activities were measured in the cytosolic and mitochondrial preparations from cerebral cortex. We verified that CK activities were significantly inhibited by DGA (11-34% inhibition) at concentrations as low as 0.25 mM, being the mitochondrial fraction the most affected activity. Kinetic studies revealed that the inhibitory effect of DGA was non-competitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of DGA on tCK activity is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of CK activity for brain metabolism homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA may be related to the neurodegeneration of patients affected by DHGA.

  11. Review on Histological and Functional Effect of Aluminium Chloride on Cerebral Cortex of the Brain

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    Birhane Alem Berihu

    2015-08-01

    Full Text Available Various findings are give emphasis to Aluminium has more and more obvious disturbance of the brain other body organs. The purpose of this review is to give a comprehensive report of the existing data on Aluminium induced brain toxicity in different animal models. Along with, we also have made an attempt to present the possible mechanism related to aluminium induced brain toxicity suggested by various researchers. We used 62 different published materials for the compilation of this review article. Google search engine was used for accessing published materials from databases like google scholar, pubmed and hinari. The focus is on Al levels in brain, region-specific and subcellular distribution, mechanism of aluminium on neurotoxicity, histological change and neurobehavioral alternations. The present analysis indicated that AlCl3 showed to be neurotoxin chemical by affecting the biochemical content of brain, histological alternation of cerebral cortex of the brain, disrupting behavioral activities. However, whether aluminium is a sole factor in neurodegeneration, histological alternation of cerebral cortex of the brain still needs to be understood.

  12. Neural convergence and divergence in the mammalian cerebral cortex: from experimental neuroanatomy to functional neuroimaging

    Science.gov (United States)

    Man, Kingson; Kaplan, Jonas; Damasio, Hanna; Damasio, Antonio

    2013-01-01

    A development essential for understanding the neural basis of complex behavior and cognition is the description, during the last quarter of the twentieth century, of detailed patterns of neuronal circuitry in the mammalian cerebral cortex. This effort established that sensory pathways exhibit successive levels of convergence, from the early sensory cortices to sensory-specific association cortices and to multisensory association cortices, culminating in maximally integrative regions; and that this convergence is reciprocated by successive levels of divergence, from the maximally integrative areas all the way back to the early sensory cortices. This article first provides a brief historical review of these neuroanatomical findings, which were relevant to the study of brain and mind-behavior relationships using a variety of approaches and to the proposal of heuristic anatomo-functional frameworks. In a second part, the article reviews new evidence that has accumulated from studies of functional neuroimaging, employing both univariate and multivariate analyses, as well as electrophysiology, in humans and other mammals, that the integration of information across the auditory, visual, and somatosensory-motor modalities proceeds in a content-rich manner. Behaviorally and cognitively relevant information is extracted from and conserved across the different modalities, both in higher-order association cortices and in early sensory cortices. Such stimulus-specific information is plausibly relayed along the neuroanatomical pathways alluded to above. The evidence reviewed here suggests the need for further in-depth exploration of the intricate connectivity of the mammalian cerebral cortex in experimental neuroanatomical studies. PMID:23840023

  13. Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

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    Ben Holmes

    2016-01-01

    Full Text Available Transcranial direct current stimulation (tDCS has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways, and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.

  14. Neural convergence and divergence in the mammalian cerebral cortex: from experimental neuroanatomy to functional neuroimaging.

    Science.gov (United States)

    Man, Kingson; Kaplan, Jonas; Damasio, Hanna; Damasio, Antonio

    2013-12-15

    A development essential for understanding the neural basis of complex behavior and cognition is the description, during the last quarter of the twentieth century, of detailed patterns of neuronal circuitry in the mammalian cerebral cortex. This effort established that sensory pathways exhibit successive levels of convergence, from the early sensory cortices to sensory-specific and multisensory association cortices, culminating in maximally integrative regions. It was also established that this convergence is reciprocated by successive levels of divergence, from the maximally integrative areas all the way back to the early sensory cortices. This article first provides a brief historical review of these neuroanatomical findings, which were relevant to the study of brain and mind-behavior relationships and to the proposal of heuristic anatomofunctional frameworks. In a second part, the article reviews new evidence that has accumulated from studies of functional neuroimaging, employing both univariate and multivariate analyses, as well as electrophysiology, in humans and other mammals, that the integration of information across the auditory, visual, and somatosensory-motor modalities proceeds in a content-rich manner. Behaviorally and cognitively relevant information is extracted from and conserved across the different modalities, both in higher order association cortices and in early sensory cortices. Such stimulus-specific information is plausibly relayed along the neuroanatomical pathways alluded to above. The evidence reviewed here suggests the need for further in-depth exploration of the intricate connectivity of the mammalian cerebral cortex in experimental neuroanatomical studies.

  15. 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.

  16. Cytoarchitecture of the human cerebral cortex: MR microscopy of excised specimens at 9.4 Tesla.

    Science.gov (United States)

    Fatterpekar, Girish M; Naidich, Thomas P; Delman, Bradley N; Aguinaldo, Juan G; Gultekin, S Humayun; Sherwood, Chet C; Hof, Patrick R; Drayer, Burton P; Fayad, Zahi A

    2002-09-01

    The laminar patterns displayed by MR microscopy (MRM) form one basis for the classification of the cytoarchitectonic areas (Brodmann areas). It is plausible that in the future MRM may depict Brodmann areas directly, and not only by inference from gross anatomic location. Our purpose was to depict the laminar cytoarchitecture of excised, formalin-fixed specimens of human cerebral cortex by use of 9.4-T MR and to correlate MR images with histologic stains of the same sections. Formalin-fixed samples of human sensory isocortex (calcarine, Heschl's, and somatosensory cortices), motor isocortex (hand motor area of M1), polar isocortex (frontal pole), allocortex (hippocampal formation), and transitional periallocortex (retrosplenial cortex) were studied by MRM at 9.4 T with intermediate-weighted pulse sequences for a total overnight acquisition time of 14 hours 17 minutes for each specimen. The same samples were then histologically analyzed to confirm the MR identification of the cortical layers. Curves representing the change in MR signal intensity across the cortex were generated to display the signal intensity profiles for each type of cortex. High-field-strength MR imaging at a spatial resolution of 78 x 78 x 500 micro m resolves the horizontal lamination of isocortex, allocortex, and periallocortex and displays specific intracortical structures such as the external band of Baillarger. The signal intensity profiles demonstrate the greatest hypointensity at the sites of maximum myelin concentration and maximum cell density and show gradations of signal intensity inversely proportional to varying cell density. MRM at 9.4 T depicts important aspects of the cytoarchitecture of normal formalin-fixed human cortex.

  17. Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M.W.

    1988-06-01

    Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with (3H)thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation.

  18. Ischemia Induces Release of Endogenous Amino Acids from the Cerebral Cortex and Cerebellum of Developing and Adult Mice

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    Simo S. Oja

    2013-01-01

    Full Text Available Ischemia enhanced release of endogenous neuroactive amino acids from cerebellar and cerebral cortical slices. More glutamate was released in adult than developing mice. Taurine release enhanced by K+ stimulation and ischemia was more than one magnitude greater than that of GABA or glutamate in the developing cerebral cortex and cerebellum, while in adults the releases were almost comparable. Aspartate release was prominently enhanced by both ischemia and K+ stimulation in the adult cerebral cortex. In the cerebellum K+ stimulation and ischemia evoked almost 10-fold greater GABA release in 3-month olds than in 7-day olds. The release of taurine increased severalfold in the cerebellum of 7-day-old mice in high-K+ media, whereas the K+-evoked effect was rather small in adults. In 3-month-old mice no effects of K+ stimulation or ischemia were seen in the release of aspartate, glycine, glutamine, alanine, serine, or threonine. The releases from the cerebral cortex and cerebellum were markedly different and also differed between developing and adult mice. In developing mice only the release of inhibitory taurine may be large enough to counteract the harmful effects of excitatory amino acids in ischemia in both cerebral cortex and cerebellum, in particular since at that age the release of glutamate and aspartate cannot be described as massive.

  19. Expression of bone morphogenetic protein 7 in the cerebral cortex of rats after ischemic-hypoxic injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Some researches demonstrate that exogenous bone morphogenetic protein 7 (BMP-7) can protect ischemic cerebral nerve tissue and promote recovery of motor energy function; however, there is lack of direct evidences of endogenous BMP-7 effect.OBJECTIVE: To observe the expression of endogenous BMP-7 in nerve tissue with ischemic-hypoxic injury and investigate the possible effects on damaged nerve tissue.DESIGN: Observational contrast animal study.SETTING: Department of Anatomy and Histoembryology, Peking University Health Science Center.MATERIALS: The experiment was carried out in the Nerve Researching Laboratory of Anatomy Department, Peking University Health Science Center from October 2006 to March 2007. A total of 25 adult male SD rats weighing 250 - 300 g and several newborn SD rats were selected from Experimental Animal Center, Peking University Health Science Center. Rabbit-anti-BMP-7 polyclonal antibody was provided by Wuhan Boster Company.METHODS: ① Adult rats were randomly divided into ischemia group (n =10), sham operation group (n =10) and normal group (n =5). Right external-internal carotid artery occlusion was used to infarct middle cerebral artery of adult rats in the ischemia group so as to copy focal cerebral infarction models. Line cork was inserted in crotch of internal and external carotid artery of adult rats in the sham operation group, while adult rats in the normal group were not given any treatments. ② Cerebral cortex of newborn rats was separated to obtain cell suspension. Cells which were cultured for 10 days were divided into control group and hypoxia/reoxygenation group. And then, cells in the hypoxia/reoxygenation group were cultured in hypoxic incubator for 4 hours and given reoxygenation for 24 hours.MAIN OUTCOME MEASURES: Immunohistochemical method was used to measure expression of BMP-7 in cerebral cortex at 24 hours after ischemia/reperfusion culture and in primary hypoxic culture.RESULTS: ① At 24 hours after

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

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    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

  1. Cerebral cortex demyelination and oligodendrocyte precursor response to experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Girolamo, Francesco; Ferrara, Giovanni; Strippoli, Maurizio; Rizzi, Marco; Errede, Mariella; Trojano, Maria; Perris, Roberto; Roncali, Luisa; Svelto, Maria; Mennini, Tiziana; Virgintino, Daniela

    2011-09-01

    Experimentally induced autoimmune encephalomyelitis (EAE) in mice provides an animal model that shares many features with human demyelinating diseases such as multiple sclerosis (MS). To what extent the cerebral cortex is affected by the process of demyelination and how the corollary response of the oligodendrocyte lineage is explicated are still not completely known aspects of EAE. By performing a detailed in situ analysis of expression of myelin and oligodendrocyte markers we have identified areas of subpial demyelination in the cerebral cortex of animals with conventionally induced EAE conditions. On EAE-affected cerebral cortices, the distribution and relative abundance of cells of the oligodendrocyte lineage were assessed and compared with control mouse brains. The analysis demonstrated that A2B5(+) glial restricted progenitors (GRPs) and NG2(+)/PDGFR-α(+) oligodendrocyte precursor cells (OPCs) were increased in number during "early" disease, 20 days post MOG immunization, whereas in the "late" disease, 39 days post-immunization, they were strongly diminished, and there was an accompanying reduction in NG2(+)/O4(+) pre-oligodendrocytes and GST-π mature oligodendrocytes. These results, together with the observed steady-state amount of NG2(-)/O4(+) pre-myelinating oligodendrocytes, suggested that oligodendroglial precursors attempted to compensate for the progressive loss of myelin, although these cells appeared to fail to complete the last step of their differentiation program. Our findings confirm that this chronic model of EAE reproduces the features of neocortex pathology in progressive MS and suggest that, despite the proliferative response of the oligodendroglial precursors, the failure to accomplish final differentiation may be a key contributing factor to the impaired remyelination that characterizes these demyelinating conditions. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nelle Lambert

    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.

  3. MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction.

    Science.gov (United States)

    Chan, Shiao Y; Hancox, Laura A; Martín-Santos, Azucena; Loubière, Laurence S; Walter, Merlin N M; González, Ana-Maria; Cox, Phillip M; Logan, Ann; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D

    2014-02-01

    The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24-28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (PMCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r(2)=0.28; PMCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development.

  4. Effect of Transcranial Magnetic Stimulation on the Expression of c-Fos and Brain-derived Neurotrophic Factor of the Cerebral Cortex in Rats with Cerebral Infarct

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiaoqiao; MEI Yuanwu; LIU Chuanyu; YU Shanchun

    2007-01-01

    The effect of transcranial magnetic stimulation (TMS) on the neurological functional recovery and expression of c-Fos and brain-derived neurotrophic factor (BDNF) of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral infarction models were established by using left middle cerebral artery occlusion (MCAO) and were randomly divided into a model group (n=40) and a TMS group (n=40). TMS treatment (2 times per day, 30 pulses per time) with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after MCAO. Modified neurological severity score (NSS) were recorded before and 1, 7, 14, 21, and 28 day(s) after MCAO. The expression of c-Fos and BDNF was immunohistochemically detected 1, 7,14, 21, and 28 day(s) after infarction respectively. Our results showed that a significant recovery of NSS (P<0.05) was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-Fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-Fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days (P<0.05) and 7,14, 21 days (P<0.01) after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS's ability to promote the expression of c-Fos and BDNF of the cerebral cortex in rats with cerebral infarction.

  5. Effect of electric acupuncture on the expression of NgR in the cerebral cortex,the medulla oblongata,and the spinal cord of hypertensive rats after cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    谭峰

    2014-01-01

    Objective To observe the effect of electric acupuncture(EA)on the Nogo receptors(NgR)protein expression in the cerebral cortex,the medulla oblongata,and the spinal cord of cerebral ischemia-reperfusion(I/R)stroke-prone renovascular hypertensive rats(RHRSP)with middle cerebral artery occlusion(MCAO)at different time points,and to investigate its possible mecha-

  6. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

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    Mathew Jobin

    2012-02-01

    Full Text Available Abstact Background Gamma amino butyric acid (GABA, the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P Aά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

  7. Collateralization of the pathways descending from the cerebral cortex to brain stem and spinal cord in cat and monkey

    NARCIS (Netherlands)

    K. Keizer (Koos)

    1989-01-01

    textabstractThe present study deals with the collateralization of the descending pathways from the cerebral cortex to the brain stem and the spinal cord in cat and monkey. The distributions of the branching cortical neurons were studied using retrograde fluorescent tracers. In addition, a new retrog

  8. Magnetic stimulation at Neiguan (PC6) acupoint increases connections between cerebral cortex regions

    Institute of Scientific and Technical Information of China (English)

    Hong-li Yu; Gui-zhi Xu; Lei Guo; Ling-di Fu; Shuo Yang; Shuo Shi; Hua Lv

    2016-01-01

    Stimulation at speciifc acupoints can activate cortical regions in human subjects. Previous studies have mainly focused on a single brain region. However, the brain is a network and many brain regions participate in the same task. The study of a single brain region alone cannot clearly explain any brain-related issues. Therefore, for the present study, magnetic stimulation was used to stimulate the Neiguan (PC6) acu-point, and 32-channel electroencephalography data were recorded before and after stimulation. Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitabil-ity. Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.

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

    Science.gov (United States)

    Hernández-Fonseca, Juan P.; Rincón, Jaimar; Pedreañez, Adriana; Viera, Ninoska; Arcaya, José L.; Carrizo, Edgardo; Mosquera, Jesús

    2009-01-01

    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. PMID:19812703

  10. Expression of the SNAT2 amino acid transporter during the development of rat cerebral cortex.

    Science.gov (United States)

    Rodríguez, Angelina; Angelina, Rodríguez; Berumen, Laura C; Francisco, Zafra; Giménez, Cecilio; Cecilio, Giménez; García-Alcocer, María Guadalupe; Guadalupe, García-Alcocer María

    2011-11-01

    The sodium-coupled neutral amino acid transporter 2 (SNAT2) is a protein that is expressed ubiquitously in mammalian tissues and that displays Na(+), voltage and pH dependent activity. This transporter mediates the passage of small zwitterionic amino acids across the cell membrane and regulates the cell homeostasis and its volume. We have examined the expression of SNAT2 mRNA and protein during the development of the rat cerebral cortex, from gestation through the postnatal stages to adulthood. Our data reveal that SNAT2 mRNA and protein expression is higher during embryogenesis, while it subsequently diminishes during postnatal development. Moreover, during embryonic period SNAT2 colocalizes with the radial glial cells marker GLAST, while in postnatal period it is mainly detected in neuronal dendrites. These findings suggest a relevant role for amino acid transport through SNAT2 in the developing embryonic brain.

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

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    Marcos R Costa

    2015-01-01

    Full Text Available 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.

  12. 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.

  13. Effect of ethanol administration and withdrawal on GABA receptor binding in rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Volicer, L.; Biagioni, T.M.

    1982-01-01

    Sodium independent GABA receptor binding was measured in synaptosomes prepared from cerebral cortex of rats made ethanol dependent by three daily ethanol administrations. In rats sacrificed 1 hour after the last ethanol dose there was a lower number of low affinity binding sites and lower affinity of the high affinity binding than in controls. The decreased affinity was present only in rats who showed symptoms of ethanol withdrawal during the course of ethanol administration. In rats sacrificed during ethanol withdrawal the affinity of the high affinity binding was lower than in controls and other binding characteristics were unchanged. This decreased binding was normalized by repeated Triton X-100 incubations indicating involvement of an endogenous inhibitor in this ethanol effect. Acute ethanol administration did not change GABA receptor binding.

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

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    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.

  15. Network and external perturbation induce burst synchronisation in cat cerebral cortex

    Science.gov (United States)

    Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Batista, Antonio M.; Baptista, Murilo S.; Viana, Ricardo L.

    2016-05-01

    The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that burst synchronisation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.

  16. 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.

  17. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

    Science.gov (United States)

    Ascoli, Giorgio A; Alonso-Nanclares, Lidia; Anderson, Stewart A; Barrionuevo, German; Benavides-Piccione, Ruth; Burkhalter, Andreas; Buzsáki, György; Cauli, Bruno; Defelipe, Javier; Fairén, Alfonso; Feldmeyer, Dirk; Fishell, Gord; Fregnac, Yves; Freund, Tamas F; Gardner, Daniel; Gardner, Esther P; Goldberg, Jesse H; Helmstaedter, Moritz; Hestrin, Shaul; Karube, Fuyuki; Kisvárday, Zoltán F; Lambolez, Bertrand; Lewis, David A; Marin, Oscar; Markram, Henry; Muñoz, Alberto; Packer, Adam; Petersen, Carl C H; Rockland, Kathleen S; Rossier, Jean; Rudy, Bernardo; Somogyi, Peter; Staiger, Jochen F; Tamas, Gabor; Thomson, Alex M; Toledo-Rodriguez, Maria; Wang, Yun; West, David C; Yuste, Rafael

    2008-07-01

    Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.

  18. 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.

  19. The subcellular distribution and properties of hexokinases in the guinea-pig cerebral cortex.

    Science.gov (United States)

    Bachelard, H S

    1967-07-01

    1. Hexokinase activities were estimated in primary subcellular fractions from guinea-pig cerebral cortex and in sucrose-density-gradient subfractions of the mitochondrial and microsomal fractions. 2. Appreciable activities were observed in mitochondrial, microsomal and soluble fractions. The activity in the mitochondrial fraction was associated with the mitochondria rather than with myelin or nerve endings and that in the microsomal fraction was associated with membrane fragments. 3. Most of the mitochondrial activity was extracted in soluble form by osmotic ;shock'. The activity of the mitochondrial extract differed from the soluble activity in kinetic properties and in electrophoretic behaviour. 4. No evidence was obtained for the presence of a high-K(m) glucokinase in the brain. 5. The results are discussed in terms of relevance to considerations of glucose utilization by the brain.

  20. The complexity of the calretinin-expressing progenitors in the human cerebral cortex

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    Nevena V Radonjic

    2014-08-01

    Full Text Available The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR+ cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR+ interneurons originate in the caudal ganglionic eminence (CGE from Gsx2+ progenitors, but in humans it has been suggested that a subpopulation of CalR+ cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ. The progenitors for cortically generated CalR+ subpopulation in primates are not yet characterized. Hence, the aim of this study was to identify patterns of expression of the transcription factors (TFs that commit cortical stem cells to the CalR fate, with a focus on Gsx2. First, we studied the expression of Gsx2 and its downstream effectors, Ascl1 and Sp8 in the cortical regions of the fetal human forebrain at midgestation. Next, we established that a subpopulation of cells expressing these TFs are proliferating in the cortical SVZ, and can be co-labeled with CalR. The presence and proliferation of Gsx2+ cells, not only in the ventral telencephalon (GE as previously reported, but also in the cerebral cortex suggests cortical origin of a subpopulation of CalR+ neurons in humans. In vitro treatment of human cortical progenitors with Sonic hedgehog (Shh, an important morphogen in the specification of interneurons, decreased levels of Ascl1 and Sp8 proteins, but did not affect Gsx2 levels. Taken together, our ex-vivo and in vitro results on human fetal brain suggest complex endogenous and exogenous regulation of TFs implied in the specification of different subtypes of CalR+ cortical interneurons.

  1. Heterogeneity of histamine H3 receptor genomic expression in the cerebral cortex of spontaneously hypertensive rat.

    Science.gov (United States)

    Shaw, J B; Cai, Q; Mtshali, C; Myles, E L; Washington, B

    2007-05-15

    Specific binding of [3H]-N-alpha-methylhistamine to homogenates from cerebral cortex tissue was analyzed in aged Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR). Scatchard plot analysis of [3H]-N-alpha-methylhistamine binding of the H3 receptor in the cerebral cortex from aged (6, 9, 12, and 16 week) SHR animals indicated that Bmax increased, respectively, 38.05 +/- 1.58, 59.63 +/- 2.48, 79.17 +/- 5.02, and 84.41 +/- 3.72 fmol/mg of protein. Binding studies using tissue from WKY rats indicated that maximal binding (Bmax) of the ligand to the receptor was not significantly altered. The analyses also yielded Kd values of 5, 7.2, 6.3 and 3.8 nM in SHR tissue respectively. Primers based on the sequence of the third intracellular loop of the H3 receptor were amplified at 35 cycles yielding several amplicons. These amplicons expressed sizes 875, 485, and 280 bp in 6 and 9 week cortical tissue from WKY animals where as in cortical tissue from 6 and 9 week SHR animals only two amplicons were expressed, 485 and 280 bp, respectively. Differences in gene expression for 12 and 16 week WKY and SHR rats were also compared using identical primers. Five amplicons were expressed in cortical tissue from 12 and 16 week WKY rats with 1000, 900, 821, 485, and 430 bp where as in 12 and 16 week SHR animals only one amplicon was expressed at 485 bp. The present results imply (1) that H3 receptor density in cortical tissue of SHR animals increases with age where as the number of the expressed amplicons of the detected H3 receptor decreases; and (2) even though a decrease in number of expressed amplicons of the H3 receptor were observed, an increase in expression of the larger amplicon (~500 bp) is evident.

  2. TRPC Channels Mediate a Muscarinic Receptor-Induced Afterdepolarization in Cerebral Cortex

    Science.gov (United States)

    Yan, Hai-Dun; Villalobos, Claudio; Andrade, Rodrigo

    2009-01-01

    Activation of muscarinic cholinergic receptors on pyramidal cells of the cerebral cortex induces the appearance of a slow afterdepolarization that can sustain autonomous spiking after a brief excitatory stimulus. Accordingly, this phenomenon has been hypothesized to allow for the transient storage of memory traces in neuronal networks. Here we investigated the molecular basis underlying the muscarinic receptor-induced afterdepolarization using molecular biological and electrophysiological strategies. We find that the ability of muscarinic receptors to induce the inward aftercurrent underlying the slow afterdepolarization is inhibited by expression of a Gαq-11 dominant negative and is also markedly reduced in a phospholipase C β1 (PLCβ1) knock-out mouse. Furthermore, we show, using a genetically encoded biosensor, that activation of muscarinic receptor induces the breakdown of phosphatidylinositol 4,5-bisphosphate in pyramidal cells. These results indicate that the Gαq-11/PLCβ1 cascade plays a key role in the ability of muscarinic receptors to signal the inward aftercurrent. We have shown previously that the muscarinic afterdepolarization is mediated by a calcium-activated nonselective cation current, suggesting the possible involvement of TRPC channels. We find that expression of a TRPC dominant negative inhibits, and overexpression of wild-type TRPC5 or TRPC6 enhances, the amplitude of the muscarinic receptor-induced inward aftercurrent. Furthermore, we find that coexpression of TRPC5 and T-type calcium channels is sufficient to reconstitute a muscarinic receptor-activated inward aftercurrent in human embryonic kidney HEK-293 cells. These results indicate that TRPC channels mediate the muscarinic receptor-induced slow afterdepolarization seen in pyramidal cells of the cerebral cortex and suggest a possible role for TRPC channels in mnemonic processes. PMID:19675237

  3. Neurotensin decreases high affinity [3H]-ouabain binding to cerebral cortex membranes.

    Science.gov (United States)

    Rosin, Carina; Ordieres, María Graciela López; Arnaiz, Georgina Rodríguez de Lores

    2011-12-10

    Previous work from this laboratory showed the ability of neurotensin to inhibit synaptosomal membrane Na(+), K(+)-ATPase activity, the effect being blocked by SR 48692, a non-peptidic antagonist for high affinity neurotensin receptor (NTS1) [López Ordieres and Rodríguez de Lores Arnaiz 2000; 2001]. To further study neurotensin interaction with Na(+), K(+)-ATPase, peptide effect on high affinity [(3)H]-ouabain binding was studied in cerebral cortex membranes. It was observed that neurotensin modified binding in a dose-dependent manner, leading to 80% decrease with 1 × 10(-4)M concentration. On the other hand, the single addition of 1 × 10(-6)M, 1 × 10(-5)M and 1 × 10(-4)M SR 48692 (Sanofi-Aventis, U.S., Inc.) decreased [(3)H]-ouabain binding (in %) to 87 ± 16; 74 ± 16 and 34 ± 17, respectively. Simultaneous addition of neurotensin and SR 48692 led to additive or synergic effects. Partial NTS2 agonist levocabastine inhibited [(3)H]-ouabain binding likewise. Saturation assays followed by Scatchard analyses showed that neurotensin increased K(d) value whereas failed to modify B(max) value, indicating a competitive type interaction of the peptide at Na(+), K(+)-ATPase ouabain site. At variance, SR 48692 decreased B(max) value whereas it did not modify K(d) value. [(3)H]-ouabain binding was also studied in cerebral cortex membranes obtained from rats injected i. p. 30 min earlier with 100 μg and 250 μg/kg SR 48692. It was observed that the 250 μg/kg SR 48692 dose led to 19% decrease in basal [(3)H]-ouabain binding. After SR 48692 treatments, addition of 1 × 10(-6)M led to additive or synergic effect. Results suggested that [(3)H]-ouabain binding inhibition by neurotensin hardly involves NTS1 receptor.

  4. Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats

    Energy Technology Data Exchange (ETDEWEB)

    Norton, S.; Kimler, B.F. (Univ. of Kansas Medical Center, Kansas City (USA))

    1990-11-01

    Pregnant rats were exposed to gamma radiation from a 137Cs irradiator on gestational Day 15. Fetuses that received 0.25, 0.5, 0.75, or 1.0 Gy were examined 24 h after irradiation for changes in the cells of the cerebral mantle of the developing brain. The extent of changes following 0.5 Gy was studied at 3, 6, 12, or 24 h after exposure. Cortical thickness of the cerebral mantle was not significantly altered. The number of pyknotic cells, number of macrophages, nuclear area, and number of mitotic cells were altered in a dose-related way. The number of pyknotic cells was significantly increased at all doses. A positive correlation between the number of pyknotic cells and the number of macrophages developed with time. At 3 h after irradiation about 60% of pyknotic cells were found in the subventricular zone and about 25% in the intermediate zone and cortical plate. The number of such cells in the upper layers of the cortex steadily increased up to 24 h, at which time about 70% of pyknotic cells were in these two layers. The relationship of the movement of pyknotic cells to migration of postmitotic neuroblasts is discussed.

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

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    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.

  6. Stage-specific requirement for cyclin D1 in glial progenitor cells of the cerebral cortex.

    Science.gov (United States)

    Nobs, Lionel; Baranek, Constanze; Nestel, Sigrun; Kulik, Akos; Kapfhammer, Josef; Nitsch, Cordula; Atanasoski, Suzana

    2014-05-01

    Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2-immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3-month-old mice. Analysis of cyclin D1-deficient mice reveals a cell and stage-specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8-month-old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant.

  7. Cerebral cortex classification by conditional random fields applied to intraoperative thermal imaging

    Directory of Open Access Journals (Sweden)

    Hoffmann Nico

    2016-09-01

    Full Text Available Intraoperative thermal neuroimaging is a novel intraoperative imaging technique for the characterization of perfusion disorders, neural activity and other pathological changes of the brain. It bases on the correlation of (sub-cortical metabolism and perfusion with the emitted heat of the cortical surface. In order to minimize required computational resources and prevent unwanted artefacts in subsequent data analysis workflows foreground detection is a important preprocessing technique to differentiate pixels representing the cerebral cortex from background objects. We propose an efficient classification framework that integrates characteristic dynamic thermal behaviour into this classification task to include additional discriminative features. The first stage of our framework consists of learning this representation of characteristic thermal time-frequency behaviour. This representation models latent interconnections in the time-frequency domain that cover specific, yet a priori unknown, thermal properties of the cortex. In a second stage these features are then used to classify each pixel’s state with conditional random fields. We quantitatively evaluate several approaches to learning high-level features and their impact to the overall prediction accuracy. The introduction of high-level features leads to a significant accuracy improvement compared to a baseline classifier.

  8. Complex events initiated by individual spikes in the human cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Gábor Molnár

    2008-09-01

    Full Text Available Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 +/- 17 ms sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes.

  9. Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex.

    Science.gov (United States)

    Tabata, Hidenori; Nakajima, Kazunori

    2003-11-05

    Two distinct modes of radial neuronal migration, locomotion and somal translocation, have been reported in the developing cerebral cortex. Although these two modes of migration have been well documented, the cortical intermediate zone contains abundant multipolar cells, and they do not resemble the cells migrating by locomotion or somal translocation. Here, we report that these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers. Time-lapse analysis of living slices revealed that the multipolar cells do not have any fixed cell polarity, and that they very dynamically extend and retract multiple processes as their cell bodies slowly move. They do not usually move straight toward the pial surface during their radial migration, but instead frequently change migration direction and rate; sometimes they even remain in almost the same position, especially when they are in the subventricular zone. Occasionally, the multipolar cells jump tangentially during their radial migration. Because the migration modality of these cells clearly differs from locomotion or somal translocation, we refer to their novel type of migration as "multipolar migration." In view of the high proportion of cells exhibiting multipolar migration, this third mode of radial migration must be an important type of migration in the developing cortex.

  10. Neuronal activity (c-Fos delineating interactions of the cerebral cortex and basal ganglia

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    Mei-Hong eQiu

    2014-03-01

    Full Text Available The cerebral cortex and basal ganglia (BG form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave EEG but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine (NMDA receptor antagonist and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist. Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN input to internal globus pallidus (GPi and substantia nigra pars reticulata (SNr, while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe, and STN but increased activity of the GPi, SNr and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders.

  11. Embedding task-based neural models into a connectome-based model of the cerebral cortex

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    Antonio Ulloa

    2016-08-01

    Full Text Available A number of recent efforts have used large-scale, biologically realistic, neural models to help understand the neural basis for the patterns of activity observed in both resting state and task-related functional neural imaging data. An example of the former is The Virtual Brain (TVB software platform, which allows one to apply large-scale neural modeling in a whole brain framework. TVB provides a set of structural connectomes of the human cerebral cortex, a collection of neural processing units for each connectome node, and various forward models that can convert simulated neural activity into a variety of functional brain imaging signals. In this paper, we demonstrate how to embed a previously or newly constructed task-based large-scale neural model into the TVB platform. We tested our method on a previously constructed large-scale neural model (LSNM of visual object processing that consisted of interconnected neural populations that represent, primary and secondary visual, inferotemporal , and prefrontal cortex. Some neural elements in the original model were 'non task-specific' (NS neurons that served as noise generators to 'task-specific' neurons that processed shapes during a delayed match-to-sample (DMS task. We replaced the NS neurons with an anatomical TVB connectome model of the cerebral cortex comprising 998 regions of interest interconnected by white matter fiber tract weights. We embedded our LSNM of visual object processing into corresponding nodes within the TVB connectome. Reciprocal connections between TVB nodes and our task-based modules were included in this framework. We ran visual object processing simulations and showed that the TVB simulator successfully replaced the noise generation originally provided by NS neurons; i.e., the DMS tasks performed with the hybrid LSNM/TVB simulator generated equivalent neural and fMRI activity to that of the original task-based models. Additionally, we found partial agreement between the

  12. 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

  13. 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.

  14. Effects of low dose x-ray on development and differentiation of cerebral cortex, 13. Observation of construction of cerebral cortex in mice irradiated at 17 days of gestational age

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, K.; Hayashi, Y.; Ito, Y.; Kameyama, Y. (Nagoya Univ. (Japan). Research Inst. of Environmental Medicine)

    1980-03-01

    ICR mice were irradiated with 25 or 100 R of x-ray at 17 days of pregnancy, and /sup 3/H-thymidine was injected immediately after the irradiation. The brain of progenies which were born from irradiated ICR mice was extracted 4 weeks after their birth, and histoautoradiography of the cerebram were made. Distribution of nerve cells labelled strongly with /sup 3/H-thymidine was observed, and the construction of cerebral cortex was discussed. Abnormality in parietal region of new cerebral cortex in which nerve cells labelled strongly with /sup 3/H-thymidine distributed was not found, but a count of nerve cells distributing tended to decrease according to exposure dose.

  15. Developmental and neurochemical features of cholinergic neurons in the murine cerebral cortex

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    Becchetti Andrea

    2009-03-01

    Full Text Available Abstract Background The existence and role of intrinsic cholinergic cells in the cerebral cortex is controversial, because of their variable localization and morphology in different mammalian species. We have applied choline acetyltransferase (ChAT immunocytochemistry to study the distribution of cholinergic neurons in the murine cerebral cortex, in the adult and during postnatal development. For more precise neurochemical identification of these neurons, the possible colocalization of ChAT with different markers of cortical neuronal populations has been analyzed by confocal microscopy. This method was also used to verify the relationship between cholinergic cells and cortical microvessels. Results ChAT positive cells appeared at the end of the first postnatal week. Their density dramatically increased at the beginning of the second postnatal week, during which it remained higher than in perinatal and adult stages. In the adult neocortex, cholinergic neurons were particularly expressed in the somatosensory area, although their density was also significant in visual and auditory areas. ChAT positive cells tended to be scarce in other regions. They were mainly localized in the supragranular layers and displayed a fusiform/bipolar morphology. The colocalization of ChAT with pyramidal neuron markers was negligible. On the other hand, more than half of the cholinergic neurons contained calretinin, but none of them expressed parvalbumin or calbindin. However, only a fraction of the ChAT positive cells during development and very few in adulthood turned out to be GABAergic, as judged from expression of GABA and its biosynthetic enzymes GAD67/65. Consistently, ChAT showed no localization with interneurons expressing green fluorescent protein under control of the GAD67 promoter in the adult neocortex. Finally, the cortical cholinergic cells often showed close association with the microvessel walls, as identified with the gliovascular marker aquaporin 4

  16. 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

  17. 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.

  18. Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2011-09-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. Tyrosinemia type II is a disorder of autosomal recessive inheritance characterized by neurological symptoms similar to those observed in patients with creatine deficiency syndromes. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study our main objective was to investigate the in vivo and in vitro effects of different concentrations and preincubation times of tyrosine on cytosolic and mitochondrial creatine kinase activities of the cerebral cortex from 14-day-old Wistar rats. The cytosolic CK was reduced by 15% at 1 mM and 32% at 2 mM tyrosine. Similarly, the mitochondrial CK was inhibited by 15% at 1 mM and 22% at 2 mM tyrosine. We observed that the inhibition caused by tyrosine was concentration-dependent and was prevented by reduced glutathione. Results also indicated that mitochondrial, but not cytosolic creatine kinase activity was inhibited by tyrosine in a time-dependent way. Finally, a single injection of L-Tyrosine methyl ester administered i.p. decreased cytosolic (31%) and mitochondrial (18%) creatine kinase activities of brain cortex from rats. Considering that creatine kinase is an enzyme dependent of thiol residues for its function and tyrosine induces oxidative stress, the results suggest that the inhibition caused by tyrosine might occur by oxidation of essential sulfhydryl groups of the enzyme. In case this also occurs in patients with tyrosinemia, it is possible that creatine kinase inhibition may contribute to the neurological dysfunction characteristic of tyrosinemia.

  19. 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.

  20. Rich club organization of macaque cerebral cortex and its role in network communication.

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    Logan Harriger

    Full Text Available Graph-theoretical analysis of brain connectivity data has revealed significant features of brain network organization across a range of species. Consistently, large-scale anatomical networks exhibit highly nonrandom attributes including an efficient small world modular architecture, with distinct network communities that are interlinked by hub regions. The functional importance of hubs motivates a closer examination of their mutual interconnections, specifically to examine the hypothesis that hub regions are more densely linked than expected based on their degree alone, i.e. forming a central rich club. Extending recent findings of rich club topology in the cat and human brain, this report presents evidence for the existence of rich club organization in the cerebral cortex of a non-human primate, the macaque monkey, based on a connectivity data set representing a collation of numerous tract tracing studies. Rich club regions comprise portions of prefrontal, parietal, temporal and insular cortex and are widely distributed across network communities. An analysis of network motifs reveals that rich club regions tend to form star-like configurations, indicative of their central embedding within sets of nodes. In addition, rich club nodes and edges participate in a large number of short paths across the network, and thus contribute disproportionately to global communication. As rich club regions tend to attract and disperse communication paths, many of the paths follow a characteristic pattern of first increasing and then decreasing node degree. Finally, the existence of non-reciprocal projections imposes a net directional flow of paths into and out of the rich club, with some regions preferentially attracting and others dispersing signals. Overall, the demonstration of rich club organization in a non-human primate contributes to our understanding of the network principles underlying neural connectivity in the mammalian brain, and further supports

  1. Effect of orphanin FQ and morphine on sodium channel current in somatosensory area of rat cerebral cortex

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Yurong Li; Shuwei Jia; Yunhong Zhang; Lanwei Cui; Lihui Qu

    2007-01-01

    BACKGROUND: Some experiments have demonstrated that injecting orphanin FQ (OFQ) into lateral ventricle, which can obviously decrease the pain threshold. It is indicated that OFQ is an anti-opiate substance. However, whether OFQ has effects on sensory neuron ion channel in cerebral cortex needs to be further studied.OBJECTIVE: To investigate the effects of OFQ, morphine or their combination on sodium channel current of somatosensory neurons in rat cerebral cortex.DESIGN: Repeated measurement trial.SETTING: Department of Physiology, Harbin Medical University.MATERIALS: Fifty healthy Wistar rats, aged 12-16 days, of either gender, were provided by the Experimental Animal Center, Second Hospital Affiliated to Harbin Medical University. OFQ was purchased from Sigma-Aldrich Company, and morphine was provided by the Shenyang First Pharmaceutical Factory.PC2C patch clamp amplifier and LabmasterTLlwere purchased from Yibo Life Science Instrument Co.,Ltd.of Huazhong University of Science and Techgnology.METHODS: This experiment was carried out in the Department of Physiology (provincial laboratory),Harbin Medical University between January 2005 and May 2006. Cortical neurons were acutely isolated from rats, and prepared into cell suspension following culture. ①Sodium channel current of somatosensory neurons in rat cerebral cortex was recorded before and after administration by whole-cell Patch clamptechnique after 50 nmol/L OFQ being added to extracellular fluid.②The amplitude of sodium channel current of somatosensory neurons in rat cerebral cortex was recorded before and after administration by the same method after 20 I mol/L morphine being added to extracellular fluid, and then the change of sodium channel current was recorded after 50 nmol/L OFQ being added.MAIN OUTCOME MEASURES: The amplitude of sodium channel current of somatosensory neurons in rat cerebral cortex following the administration of OFQ, morphine separately or their combination

  2. Htr2a gene and 5-HT2A receptor expression in the cerebral cortex studied using genetically modified mice

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    Rodrigo Andrade

    2010-08-01

    Full Text Available Serotonin receptors of the 5-HT2A subtype are robustly expressed in the cerebral cortex where they have been implicated in the pathophysiology and therapeutics of mental disorders and the actions of hallucinogens. Much less is known, however, about the specific cell types expressing 5-HT2A receptors in cortex. In the current study we use immunohistochemical and electrophysiological approaches in genetically modified mice to address the expression of the Htr2a gene and 5-HT2A receptors in cortex. We first use an EGFP expressing BAC transgenic mice and identify three main Htr2A gene expressing neuronal populations in cortex. The largest of these cell populations corresponds to layer V pyramidal cells of the anterior cortex, followed by GABAergic interneurons of the middle layers, and nonpyramidal cells of the subplate/Layer VIb. We then use 5-HT2A receptor knockout mice to identify an antibody capable of localizing 5-HT2A receptors in brain and use it to map these receptors. We find strong laminar expression of 5-HT2A receptors in cortex, especially along a diffuse band overlaying layer Va. This band exhibits a strong anteroposterior gradient that closely matches the localization of Htr2A expressing pyramidal cells of layer V. Finally we use electrophysiological and immunohistochemical approaches to show that most, but not all, GABAergic interneurons of the middle layers are parvalbumin expressing Fast-spiking interneurons and that these cells are depolarized and excited by serotonin, most likely through the activation of 5-HT2A receptors. These results clarify and extend our understanding of the cellular distribution of 5-HT2A receptors in the cerebral cortex.

  3. The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons

    DEFF Research Database (Denmark)

    Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta

    2017-01-01

    prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect...... that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry....

  4. 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.

  5. The Effects of Kinesio Taping on Potential in Chronic Low Back Pain Patients Anticipatory Postural Control and Cerebral Cortex

    OpenAIRE

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

    2013-01-01

    [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 elec...

  6. What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus

    OpenAIRE

    Fjell, Anders M.; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B.

    2014-01-01

    What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal reg...

  7. Electrical Stimulation of the Human Cerebral Cortex by Extracranial Muscle Activity: Effect Quantification With Intracranial EEG and FEM Simulations

    Science.gov (United States)

    Lahr, Jacob; Vorwerk, Johannes; Lucka, Felix; Aertsen, Ad; Wolters, Carsten Hermann; Schulze-Bonhage, Andreas; Ball, Tonio

    2017-01-01

    Objective Electric fields (EF) of approx. 0.2 V/m have been shown to be sufficiently strong to both modulate neuronal activity in the cerebral cortex and have measurable effects on cognitive performance. We hypothesized that the EF caused by the electrical activity of extracranial muscles during natural chewing may reach similar strength in the cerebral cortex and hence might act as an endogenous modality of brain stimulation. Here, we present first steps toward validating this hypothesis. Methods Using a realistic volume conductor head model of an epilepsy patient having undergone intracranial electrode placement and utilizing simultaneous intracranial and extracranial electrical recordings during chewing, we derive predictions about the chewing-related cortical EF strength to be expected in healthy individuals. Results We find that in the region of the temporal poles, the expected EF strength may reach amplitudes in the order of 0.1–1 V/m. Conclusion The cortical EF caused by natural chewing could be large enough to modulate ongoing neural activity in the cerebral cortex and influence cognitive performance. Significance The present study lends first support for the assumption that extracranial muscle activity might represent an endogenous source of electrical brain stimulation. This offers a new potential explanation for the puzzling effects of gum chewing on cognition, which have been repeatedly reported in the literature. PMID:27448334

  8. Histogenetic disorders of cerebral cortex induced by in utero exposure to low-doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fushiki, Shinji; Kinoshita, Chikako [Kyoto Prefectural Univ. of Medicine (Japan). Research Inst. for Neurological Diseases and Geriatrics; Hyodo-Taguchi, Yasuko; Ishikawa, Yuji; Hirobe, Tomohisa

    1999-06-01

    To elucidate the short- and long-term effects of low-level ionizing radiation on cell migration in the developing cerebral cortex of mice and rats, we irradiated them at the middle of cortical histogenesis with either {gamma}-rays or X-rays. We have demonstrated an effect of ionizing radiation on neuronal migration at doses as low as 0.15 Gy together with a changing pattern of expression of the neural cell adhesion molecule N-CAM. Our findings suggest a possible role of N-CAM in neuronal migration and suggest the presence of a threshold in terms of the effects of small radiation doses on the developing cerebral cortex. In addition, the effects of radiation on neuronal migration during the embryonic stage remained even after birth in that aberrantly placed neurons were noted in the cerebral cortex. However, such derangement was less pronounced in mature animals compared to younger ones. These observations suggest that some modification process including apoptosis might have occurred during the postnatal period. In this review, molecular pathogenesis of neuronal migration disorders will also be discussed, based upon recent experimental as well as molecular genetic studies. (author)

  9. Electrical Stimulation of the Human Cerebral Cortex by Extracranial Muscle Activity: Effect Quantification With Intracranial EEG and FEM Simulations.

    Science.gov (United States)

    Fiederer, Lukas Dominique Josef; Lahr, Jacob; Vorwerk, Johannes; Lucka, Felix; Aertsen, Ad; Wolters, Carsten Hermann; Schulze-Bonhage, Andreas; Ball, Tonio

    2016-12-01

    Electric fields (EF) of approx. 0.2 V/m have been shown to be sufficiently strong to both modulate neuronal activity in the cerebral cortex and have measurable effects on cognitive performance. We hypothesized that the EF caused by the electrical activity of extracranial muscles during natural chewing may reach similar strength in the cerebral cortex and hence might act as an endogenous modality of brain stimulation. Here, we present first steps toward validating this hypothesis. Using a realistic volume conductor head model of an epilepsy patient having undergone intracranial electrode placement and utilizing simultaneous intracranial and extracranial electrical recordings during chewing, we derive predictions about the chewing-related cortical EF strength to be expected in healthy individuals. We find that in the region of the temporal poles, the expected EF strength may reach amplitudes in the order of 0.1-1 V/m. The cortical EF caused by natural chewing could be large enough to modulate ongoing neural activity in the cerebral cortex and influence cognitive performance. The present study lends first support for the assumption that extracranial muscle activity might represent an endogenous source of electrical brain stimulation. This offers a new potential explanation for the puzzling effects of gum chewing on cognition, which have been repeatedly reported in the literature.

  10. Treatment with dehydroepiandrosterone increases peripheral benzodiazepine receptors of mitochondria from cerebral cortex in D-galactose-induced aged rats.

    Science.gov (United States)

    Chen, Chunfu; Lang, Senyang; Zuo, Pingping; Yang, Nan; Wang, Xiangqing

    2008-12-01

    The aim of this study was to determine whether dehydroepiandrosterone (DHEA) could regulate the expression of peripheral benzodiazepine receptors of mitochondria in cerebral cortex. The rats were divided into five groups. Those, in the vehicle-physiological or senescent group, received physiological or d-galactose (subcutaneously) once a day. Rats, in the vehicle-dimethyl sulfoxide- or DHEA-treated senescent group, received 2% of dimethyl sulfoxide or DHEA (intraperitoneally) every other day besides D-galactose (subcutaneously) once a day. Rats in the DHEA-treated normal group received physiological once a day and DHEA every other day. After 8-week, spatial learning was assessed for 5 days by water maze methods. Following behavioural testing, the cerebral cortex mitochondria were purified for PK11195 binding analysis. When compared to the respective vehicle, D-galactose alone induced a significant impairment in water maze performance accompanied by a reduction (30.7%) in peripheral benzodiazepine receptor density of mitochondria, and DHEA displayed a significant enhancement in learning memory accompanied by the elevation (18.3%) of peripheral benzodiazepine receptor density but not affinity in senescent rats. DHEA showed insignificant effects on both learning/memory ability and peripheral benzodiazepine receptors in normal rats when compared to physiological saline. These results suggest that chronic treatment with DHEA enhance cognitive function and increase peripheral benzodiazepine receptor density in cerebral cortex mitochondria in middle-aged senescent rats.

  11. 1Identification of genes differentially expressed in the embryonic pig cerebral cortex before and after appearance of gyration

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    Jørgensen Arne L

    2010-05-01

    Full Text Available Abstract Background Mammalian evolution is characterized by a progressive expansion of the surface area of the cerebral cortex, an increase that is accompanied by gyration of the cortical surface. The mechanisms controlling this gyration process are not well characterized but mutational analyses indicate that genes involved in neuronal migration play an important function. Due to the lack of gyration of the rodent brain it is important to establish alternative models to examine brain development during the gyration process. The pig brain is gyrated and accordingly is a candidate alternative model. Findings In this study we have identified genes differentially expressed in the pig cerebral cortex before and after appearance of gyration. Pig cortical tissue from two time points in development representing a non-folded, lissencephalic, brain (embryonic day 60 and primary-folded, gyrencephalic, brain (embryonic day 80 were examined by whole genome expression microarray studies. 91 differentially expressed transcripts (fold change >3 were identified. 84 transcripts were annotated and encoding proteins involved in for example neuronal migration, calcium binding, and cytoskeletal structuring. Quantitative real-time PCR was used to confirm the regulation of a subset of the identified genes. Conclusion This study provides identification of genes which are differentially expressed in the pig cerebral cortex before and after appearance of brain gyration. The identified genes include novel candidate genes which could have functional importance for brain development.

  12. Effects of sericin on heme oxygenase-1 expression in the hippocampus and cerebral cortex of type 2 diabetes mellitus rats

    Institute of Scientific and Technical Information of China (English)

    Zhihona Chen; Yaqiang He; Wenliang Fu; Jingfeng Xue

    2011-01-01

    Previous studies have demonstrated that sericin effectively reduces blood glucose, and protects islet cells, as well as the gonads and kidneys. However, whether sericin improves diabetes mellitus-induced structural and functional problems in the central nervous system remains poorly understood. Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin. The present study observed histological changes in the hippocampus and cerebral cortex, as well as heme oxygenase-1 expression, and explored sericin effects on the central nervous system in diabetic rats. Pathological damage to neural cells in the rat hippocampus and cerebral cortex was relieved following intragastric administration of sericin at a dose of 2.4 g/kg for 35 consecutive days. Heme oxygenase-1 protein and mRNA expressions were decreased in the hippocampus and cerebral cortex of diabetes mellitus rats after sericin treatment. The results suggest that sericin plays a protective effect on the nervous system by decreasing the high expression of heme oxygenase-1 following diabetes mellitus.

  13. Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats.

    Science.gov (United States)

    Roseni Mundstock Dias, Glaecir; Medeiros Golombieski, Ronaldo; de Lima Portella, Rafael; Pires do Amaral, Guilherme; Antunes Soares, Félix; Teixeira da Rocha, João Batista; Wayne Nogueira, Cristina; Vargas Barbosa, Nilda

    2014-01-01

    Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state. © 2014 S. Karger AG, Basel.

  14. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

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    Heqin Zhan

    2014-01-01

    Full Text Available Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF and neurotrophin-3 (NT-3 were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05 , P < 0.01. LGB significantly increased NGF and NT-3 mRNA (messenger RNA and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01. Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.

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

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    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.

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

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    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.

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

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    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.

  18. Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2012-05-01

    Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism, especially in tyrosinemia type II, which is caused by deficiency of tyrosine aminotransferase and provokes eyes, skin, and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in this study, we investigated the in vivo and in vitro effects of tyrosine on some parameters of energy metabolism in cerebral cortex of 14-day-old Wistar rats. We observed that 2 mM tyrosine inhibited in vitro the pyruvate kinase (PK) activity and that this inhibition was prevented by 1 mM reduced glutathione with 30, 60, and 90 min of preincubation. Moreover, administration of tyrosine methyl ester (TME) (0.5 mg/g of body weight) decreased the activity of PK and this reduction was prevented by pre-treatment with creatine (Cr). On the other hand, tyrosine did not alter adenylate kinase (AK) activity in vitro, but administration of TME enhanced AK activity not prevented by Cr pre-treatment. Finally, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions and this diminution was prevented by Cr pre-treatment. The results suggest that tyrosine alters essential sulfhydryl groups necessary for CK and PK functions, possibly through oxidative stress. In case this also occurs in the patients, it is possible that energy metabolism alterations may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias.

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

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    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.

  20. Proteomic analysis of rat cerebral cortex, hippocampus and striatum after exposure to morphine.

    Science.gov (United States)

    Bierczynska-Krzysik, Anna; Pradeep John, Julius Paul; Silberring, Jerzy; Kotlinska, Jolanta; Dylag, Tomasz; Cabatic, Maureen; Lubec, Gert

    2006-10-01

    Although a series of proteins in the brain have been shown to be qualitatively or quantitatively dysregulated following morphine administration, a systematic proteomic study has not been carried out so far. We therefore aimed to show the effect of morphine on protein levels in the rat brain. For this purpose rats were given a morphine base in subcutaneously placed pellets and subsequently the cerebral cortex, hippocampus and striatum were taken for proteomic studies after three days. Extracted proteins were run on two-dimensional gel electrophoresis, scanned and quantified by specific software. Proteins with significantly different levels were analysed by mass spectrometry (MALDI-TOF-TOF). Twenty-six proteins were found to be differentially expressed and were unambiguously identified. Dysregulated proteins were from several protein pathways and cascades including signaling, metabolic, protein handling, antioxidant and miscellaneous classes. These findings represent an initial approach to the generation of a 'morphinome' and may form the basis for further protein chemical studies as a valuable analytical tool. Moreover, the study reveals morphine-regulated proteins in different brain areas and indicates the pathways involved following morphine administration in the rat, the main species for pharmacological studies in the field.

  1. The effect of intervention according to muscle contraction type on the cerebral cortex of the elderly

    Science.gov (United States)

    Kang, Jeong-il; Jeong, Dae-Keun; Choi, Hyun

    2016-01-01

    [Purpose] Here we investigated the activity of the cerebral cortex after resistance training in the elderly. We evaluated the clinical neuropsychological basis of 2 contractile types, and determined the usefulness of a movement-related cortical potential (MRCP) from an electroencephalography (EEG). [Subjects and Methods] The subjects were 11 females and 11 males aged between 65 and 70 years. The subjects were randomly assigned into a group that performed an eccentric contraction exercise (experimental group I, n=11) and a group that performed a concentric contraction exercise (experimental group II, n=11). We measured activities of the rectus femoris, vastus medialis, and vastus lateralis in the non-dominant lower extremity by using surface electromyography (EMG), and measured brain activity using EEG before conducting an intervention. An intervention was conducted 40 minutes per session, once a day, 3 times a week for 4 weeks. [Results] After the intervention, activity in C4, the Cz area and rectus femoris were significantly different. [Conclusion] Our results demonstrate that MRCP from an EEG has the advantage of being non-invasive and cost-effective. Nonetheless, prospective studies are needed to reveal the specific mechanism underlying eccentric contraction exercise, which can provide baseline data for research related to aging and neural plasticity. PMID:27799694

  2. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    Science.gov (United States)

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  3. RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex.

    Science.gov (United States)

    Ohtaka-Maruyama, Chiaki; Hirai, Shinobu; Miwa, Akiko; Heng, Julian Ik-Tsen; Shitara, Hiroshi; Ishii, Rie; Taya, Choji; Kawano, Hitoshi; Kasai, Masataka; Nakajima, Kazunori; Okado, Haruo

    2013-02-21

    Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58(-/-) neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Cre-mediated deletion of RP58 using in utero electroporation in RP58(flox/flox) mice revealed that RP58 functions in cell-autonomous multipolar-to-bipolar transition, independent of cell-cycle exit. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway; Ngn2 knockdown rescued migration defects of the RP58(-/-) neurons. Our findings highlight the critical role of RP58 in multipolar-to-bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex.

  4. The role of reelin in the development and evolution of the cerebral cortex

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    Tissir F.

    2002-01-01

    Full Text Available Reelin is an extracellular matrix protein that is defective in reeler mutant mice and plays a key role in the organization of architectonic patterns, particularly in the cerebral cortex. In mammals, a "reelin signal" is activated when reelin, secreted by Cajal-Retzius neurons, binds to receptors of the lipoprotein receptor family on the surface of cortical plate cells, and triggers Dab1 phosphorylation. As reelin is a key component of cortical development in mammals, comparative embryological studies of reelin expression were carried out during cortical development in non-mammalian amniotes (turtles, squamates, birds and crocodiles in order to assess the putative role of reelin during cortical evolution. The data show that reelin is present in the cortical marginal zone in all amniotes, and suggest that reelin has been implicated in the evolution of the radial organization of the cortical plate in the synapsid lineage leading from stem amniotes to mammals, as well as in the lineage leading to squamates, thus providing an example of homoplastic evolution (evolutionary convergence. The mechanisms by which reelin instructs radial cortical organization in these two lineages seem different: in the synapsid lineage, a drastic amplification of reelin production occurred in Cajal-Retzius cells, whereas in squamates, in addition to reelin-secreting cells in the marginal zone, a second layer of reelin-producing cells developed in the subcortex. Altogether, our results suggest that the reelin-signaling pathway has played a significant role in shaping the evolution of cortical development.

  5. A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

    Science.gov (United States)

    Markov, N. T.; Ercsey-Ravasz, M. M.; Ribeiro Gomes, A. R.; Lamy, C.; Magrou, L.; Vezoli, J.; Misery, P.; Falchier, A.; Quilodran, R.; Gariel, M. A.; Sallet, J.; Gamanut, R.; Huissoud, C.; Clavagnier, S.; Giroud, P.; Sappey-Marinier, D.; Barone, P.; Dehay, C.; Toroczkai, Z.; Knoblauch, K.; Van Essen, D. C.; Kennedy, H.

    2014-01-01

    Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks. PMID:23010748

  6. 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...

  7. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  8. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  9. [Effect of rabies virus infection on the expression of parvalbumin, calbindin and calretinin in mouse cerebral cortex].

    Science.gov (United States)

    Torres-Fernández, Orlando; Yepes, Gloria E; Gómez, Javier E; Pimienta, Hernán J

    2004-03-01

    Some clinical features of rabies and experimental evidence from cell culture and laboratory animals suggest impairment of gabaergic neurotransmission. Several types of gabaergic neurons occur in the cerebral cortex. They can be identified by three neuronal markers: the calcium binding proteins (CaBPs) parvalbumin (PV), calbindin (CB) and calretinin (CR). Rabies virus spreads throughout the cerebral cortex; however, rabies cytopathic effects on gabaergic neurons are unknown. The expression of calcium-binding proteins (CaBPs) parvalbumin (PV), calbindin (CB) and calretinin (CR) was studied in the frontal cortex of mice. The effect of gabaergic neurons was evaluated immunohistochemically. The distribution patterns of CaBPs in normal mice and in mice infected with 'fixed' or 'street' rabies virus were compared. PV was found in multipolar neurons located in all cortical layers except layer I, and in pericellular clusters of terminal knobs surrounding the soma of pyramidal neurons. CB-immunoreactivity was distributed in two cortical bands. One was composed of round neurons enclosed by a heavily labeled neuropil; this band corresponds to supragranular layers II and III. The other was a weakly stained band of neuropil which contained scattered multipolar CB-ir neurons; this corresponds to infragranular layers V and VI. The CR-ir neurons were bipolar fusiform cells located in all layers of cortex, but concentrated in layers II and III. A feature common to samples infected with both types of viruses was a more intense immunoreactivity to PV in contrast to normal samples. The infection with 'street' virus did not cause additional changes in the expression of CaBPs. However, the infection with 'fixed' virus produced a remarkable reduction of CB-immunoreactivity demonstrated by the loss of CB-ir neurons and low neuropil stain in the frontal cortex. In addition, the size of CR-ir neurons in the cingulate cortex was decreased.

  10. Hemodynamic changes in a rat parietal cortex after endothelin-1-induced middle cerebral artery occlusion monitored by optical coherence tomography

    Science.gov (United States)

    Liu, Jian; Ma, Yushu; Dou, Shidan; Wang, Yi; La, Dongsheng; Liu, Jianghong; Ma, Zhenhe

    2016-07-01

    A blockage of the middle cerebral artery (MCA) on the cortical branch will seriously affect the blood supply of the cerebral cortex. Real-time monitoring of MCA hemodynamic parameters is critical for therapy and rehabilitation. Optical coherence tomography (OCT) is a powerful imaging modality that can produce not only structural images but also functional information on the tissue. We use OCT to detect hemodynamic changes after MCA branch occlusion. We injected a selected dose of endothelin-1 (ET-1) at a depth of 1 mm near the MCA and let the blood vessels follow a process first of occlusion and then of slow reperfusion as realistically as possible to simulate local cerebral ischemia. During this period, we used optical microangiography and Doppler OCT to obtain multiple hemodynamic MCA parameters. The change trend of these parameters from before to after ET-1 injection clearly reflects the dynamic regularity of the MCA. These results show the mechanism of the cerebral ischemia-reperfusion process after a transient middle cerebral artery occlusion and confirm that OCT can be used to monitor hemodynamic parameters.

  11. Structure and plasticity potential of neural networks in the cerebral cortex

    Science.gov (United States)

    Fares, Tarec Edmond

    In this thesis, we first described a theoretical framework for the analysis of spine remodeling plasticity. We provided a quantitative description of two models of spine remodeling in which the presence of a bouton is either required or not for the formation of a new synapse. We derived expressions for the density of potential synapses in the neuropil, the connectivity fraction, which is the ratio of actual to potential synapses, and the number of structurally different circuits attainable with spine remodeling. We calculated these parameters in mouse occipital cortex, rat CA1, monkey V1, and human temporal cortex. We found that on average a dendritic spine can choose among 4-7 potential targets in rodents and 10-20 potential targets in primates. The neuropil's potential for structural circuit remodeling is highest in rat CA1 (7.1-8.6 bits/mum3) and lowest in monkey V1 (1.3-1.5 bits/mum 3 We next studied the role neuron morphology plays in defining synaptic connectivity. As previously stated it is clear that only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, ). We also evaluated the lower bound of neuron selectivity in the choice of synaptic partners. Post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21-30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7-15% of encountered axons. We next studied the role neuron morphology plays in defining synaptic connectivity. As previously stated it is clear that only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, such axo-dendritic oppositions, or potential synapses, must be bridged by dendritic spines to form synaptic connections. To explore the rules by which synaptic connections are formed within

  12. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Silva, J.E.; Matthews, P.S.

    1984-09-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.

  13. Human cerebral cortex Cajal-Retzius neuron: development, structure and function. A Golgi study.

    Science.gov (United States)

    Marín-Padilla, Miguel

    2015-01-01

    The development, morphology and possible functional activity of the Cajal-Retzius cell of the developing human cerebral cortex are explored herein. The C-RC, of extracortical origin, is the essential neuron of the neocortex first lamina. It receives inputs from afferent fibers that reach the first lamina early in development. Although the origin and function of these original afferent fibers remain unknown, their target is the first lamina sole neuron: the C-RC. This neuron orchestrates the arrival, size and stratification of all pyramidal neurons (of ependymal origin) of the neocortex gray matter. Its axonic terminals spread radially and horizontally throughout the entirety of the 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 neuronal' body 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 neocortex while their axonic collaterals will spread throughout its more recent ones and eventually will extend to great majority of the cortical surface. The neocortex first lamina evolution and composition and that of the C-RC are intertwined and mutually interdependent. It is not possible to understand the C-RC evolving morphology without understanding that of the first lamina. The first lamina composition and its structural and functional organizations obtained with different staining methods may be utterly different. These differences have added unnecessary confusion about its nature. The essential emptiness observed in hematoxylin and eosin preparations (most commonly used) contrast sharply with the concentration of dendrites (the cortex' largest) obtained using special (MAP-2) stain for dendrites. Only Golgi preparations

  14. A study of the spatial protein organization of the postsynaptic density isolated from porcine cerebral cortex and cerebellum.

    Science.gov (United States)

    Yun-Hong, Yen; Chih-Fan, Chuang; Chia-Wei, Chang; Yen-Chung, Chang

    2011-10-01

    Postsynaptic density (PSD) is a protein supramolecule lying underneath the postsynaptic membrane of excitatory synapses and has been implicated to play important roles in synaptic structure and function in mammalian central nervous system. Here, PSDs were isolated from two distinct regions of porcine brain, cerebral cortex and cerebellum. SDS-PAGE and Western blotting analyses indicated that cerebral and cerebellar PSDs consisted of a similar set of proteins with noticeable differences in the abundance of various proteins between these samples. Subsequently, protein localization in these PSDs was analyzed by using the Nano-Depth-Tagging method. This method involved the use of three synthetic reagents, as agarose beads whose surface was covalently linked with a fluorescent, photoactivable, and cleavable chemical crosslinker by spacers of varied lengths. After its application was verified by using a synthetic complex consisting of four layers of different proteins, the Nano-Depth-Tagging method was used here to yield information concerning the depth distribution of various proteins in the PSD. The results indicated that in both cerebral and cerebellar PSDs, glutamate receptors, actin, and actin binding proteins resided in the peripheral regions within ∼ 10 nm deep from the surface and that scaffold proteins, tubulin subunits, microtubule-binding proteins, and membrane cytoskeleton proteins found in mammalian erythrocytes resided in the interiors deeper than 10 nm from the surface in the PSD. Finally, by using the immunoabsorption method, binding partner proteins of two proteins residing in the interiors, PSD-95 and α-tubulin, and those of two proteins residing in the peripheral regions, elongation factor-1α and calcium, calmodulin-dependent protein kinase II α subunit, of cerebral and cerebellar PSDs were identified. Overall, the results indicate a striking similarity in protein organization between the PSDs isolated from porcine cerebral cortex and cerebellum

  15. Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment.

    Science.gov (United States)

    Awadalla, Eatemad A; Salah-Eldin, Alaa-Eldin

    2016-08-01

    Tramadol abuse is one of the most frequent health problems in Egypt and worldwide. In most cases, tramadol abused by men face a problem with premature ejaculation. Tramadol like other opioids induces a decrease in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against oxidative damage. The present work aimed to study the possible deleterious effects of oral administration of tramadol on brain and lung tissues in rats. Twenty adult male albino rats were divided into two groups; a control administered with normal saline and tramadol-treated (40mg/kg b.w.) group for 20 successive days. At the end of experimental period, blood was collected and specimens from brains and lungs were taken for histopathological and molecular studies. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities were measured in serum of control and tramadol-treated groups. Brain and lung specimens were histopathological evaluated using light microscopy. The expression levels of apoptotic related genes; Bcl-2, Bax and Caspase-3 were study in brain and lung tissues using RT-PCR analysis. We recorded a significant increase MDA level, while antioxidant enzymes; GSH, SOD and CAT were significantly decreased after tramadol-treatment. The obtained results revealed that tramadol induced a remarkable histomorphological changes in rats' brains (cerebral cortex and hippocampus) and severe histopathological changes in rats' lung when compared to that of control. On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues. Our data confirmed the risk of increased oxidative stress, neuronal and pulmonary damage due to tramadol abuse. Although tramadol is reported to be effective in pain management, its toxicity should

  16. Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy.

    Science.gov (United States)

    Friel, Kathleen M; Kuo, Hsing-Ching; Fuller, Jason; Ferre, Claudio L; Brandão, Marina; Carmel, Jason B; Bleyenheuft, Yannick; Gowatsky, Jaimie L; Stanford, Arielle D; Rowny, Stefan B; Luber, Bruce; Bassi, Bruce; Murphy, David L K; Lisanby, Sarah H; Gordon, Andrew M

    2016-10-01

    Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP.

  17. Developmental expression of parvalbumin mRNA in the cerebral cortex and hippocampus of the rat.

    Science.gov (United States)

    de Lecea, L; del Río, J A; Soriano, E

    1995-08-01

    Parvalbumin (PARV) belongs to the family of calcium-binding proteins bearing the EF hand domain. Immunocytochemical studies in the cerebral cortex have demonstrated that neurons containing PARV include two types of GABAergic interneurons, namely, basket and axo-axonic chandelier cells. The present study examines the onset and pattern of PARV mRNA expression during the development of rat neocortex and hippocampus by means of 'in situ' hybridization with an oligonucleotide probe corresponding to rat PARV cDNA. In animals aged P0-P6 no signal was detected above background in neocortex or hippocampus. At P8, a few cortical cells displayed a number of silver grains just above background levels. By P10 PARV mRNA-expressing cells in the neocortex were detected almost exclusively in layer V of somatosensory, frontal and cingulate cortices. At P12 PARV mRNA was mainly detected in layers IV, V and VIa. By P14 there was a marked overall increase in the entire neocortex, including layer II-III, both in the number of cells and in their intensity of labelling. Further maturation in the pattern of PARV mRNA concentration was observed between P16 and P21. In the hippocampus low hybridization was observed at P10-P12. In subsequent stages both the number of positive cells and the intensity of labelling increased steadily. No clear-cut radial gradients for the expression of PARV mRNA were observed in the hippocampal region. Our results show that the developmental radial gradient followed by PARV mRNA expression in the neocortex does not follow an 'inside-out' gradient, consistent with previous immunocytochemical findings. Taken together, these data indicate that the developmental sequence followed by the PARV protein directly reflects mRNA abundance and suggest that PARV mRNA expression correlates with the functional maturation of cortical interneurons.

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

    Science.gov (United States)

    Pillay, Siveshigan; Vizuete, Jeannette; Liu, Xiping; Juhasz, Gabor; Hudetz, Anthony G

    2014-01-01

    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 × 10(3) bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 × 10(3) 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.

  19. 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.

  20. Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

    Science.gov (United States)

    Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

    2013-06-01

    Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

  1. Exposure to diphenyl ditelluride, via maternal milk, causes oxidative stress in cerebral cortex, hippocampus and striatum of young rats

    Energy Technology Data Exchange (ETDEWEB)

    Stangherlin, Eluza Curte; Ardais, Ana Paula; Rocha, Joao Batista Teixeira; Nogueira, Cristina Wayne [Universidade Federal de Santa Maria, Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Santa Maria, RS (Brazil)

    2009-05-15

    The present study evaluated the effect of diphenyl ditelluride [(PhTe){sub 2}] exposure to mothers on the cerebral oxidative status of their offspring. The dams received (PhTe){sub 2} or canola oil via subcutaneous injection once daily during the first 14 days of lactational period. At post natal day 28, biochemical parameters of oxidative stress were evaluated in cerebral structures - cortex, hippocampus and striatum - of young rats. Exposure to (PhTe){sub 2} increased lipid peroxidation levels and inhibited {delta}-ALA-D, catalase and SOD activities in hippocampus and striatum of young rats. (PhTe){sub 2} induced changes in the levels of non-enzymatic antioxidant defenses in cortex and striatum of young rats. The exposure to (PhTe){sub 2}, via maternal milk, caused oxidative stress in cerebral structures of young rats. Thus, the possible role of disrupted prooxidant/antioxidant balance in (PhTe){sub 2} toxicity was demonstrated. These results highlighted a possible molecular mechanism involved in toxicity caused by (PhTe){sub 2}. (orig.)

  2. 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

    2017-01-01

    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. PMID:28280411

  3. 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.

  4. LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex.

    Science.gov (United States)

    Nimmervoll, Birgit; White, Robin; Yang, Jenq-Wei; An, Shuming; Henn, Christopher; Sun, Jyh-Jang; Luhmann, Heiko J

    2013-07-01

    During the pre- and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor α and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.

  5. PSA-NCAM is expressed in immature, but not recently generated, neurons in the adult cat cerebral cortex layer II

    Directory of Open Access Journals (Sweden)

    Emilio eVarea

    2011-02-01

    Full Text Available Neuronal production persists during adulthood in the dentate gyrus and the olfactory bulb, where substantial numbers of immature neurons can be found. These cells can also be found in the paleocortex layer II of adult rodents, but in this case most of them have been generated during embryogenesis. Recent reports have described the presence of similar cells, with a wider distribution, in the cerebral cortex of adult cats and primates and have suggested that they may develop into interneurons. The objective of this study is to verify this hypothesis and to explore the origin of these immature neurons in adult cats. We have analysed their distribution using immunohistochemical analysis of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM and their phenotype using markers of mature neurons and different interneuronal populations. Additionally, we have explored the origin of these cells administering 5'bromodeoxyuridine (5’BrdU during adulthood. Immature neurons were widely dispersed in the cerebral cortex layers II and upper III, being specially abundant in the piriform and entorhinal cortices, in the ventral portions of the frontal and temporoparietal lobes, but relatively scarce in dorsal regions, such as the primary visual areas. Only a small fraction of PSA-NCAM expressing cells in layer II expressed the mature neuronal marker NeuN and virtually none of them expressed calcium binding proteins or neuropeptides. By contrast, most, if not all of these cells expressed the transcription factor Tbr-1, specifically expressed by pallium-derived principal neurons, but not CAMKII, a marker of mature excitatory neurons. Absence of PSA-NCAM/5’BrdU co-localization suggests that, as in rats, these cells were not generated during adulthood. Together, these results indicate that immature neurons in the adult cat cerebral cortex layer II are not recently generated and that they may differentiate into principal neurons.

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

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    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.

  7. The Distribution of MAP-2 Phosphorylation in Cerebral Cortex of Long-Tailed Monkey Fetuses (Macaca fascicularis in the Last Trimester of Gestation

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    Tri Wahyu Pangestiningsih

    2015-11-01

    Full Text Available Memories are storage in cholinoceptive cells, the cells which are enriched with microtubule-associated protein 2 (MAP-2 that localized in the neuronal dendrite and the cell bodies. Phosphorylation of MAP-2 may increase memory with reduce stability of dendrite by altered dendrite length and lead new side-branches of neuronal as a neuronal plasticity processes in cerebral cortex. The aim of this research is to study the distribution of MAP-2 phosphorylation neurons in cerebral cortex of long-tailed macaques in the third semester of gestationalimmunohistochemically using avidin biotin conjugated complex method. Neurons MAP-2 phosphorylation immunoreactive were located in dendrites and cell bodies, mostly in pyramidal neurons of cerebral cortex. Intensity of MAP-2 phosphorylation immunoreactivity in layer V were stronger than another layer and the neurons that very intensely stained were the pyramidal cells in frontal and parietal lobes, that was suggested that neurons in this areas more responsive to neuroplasticity. From the results we concluded that MAP-2 phosphorylation already distributed in the cerebral cortex of long-tailed macaque fetuses at the last trimester of gestation, mostly in the pyramidal cells of layer V that is suggested plays a role for preparation of memoryformation.Keywords: fetus, long-tailed monkey, cerebral cortex, memory, MAP-2 phosphorylation

  8. Hyperlexia and ambient echolalia in a case of cerebral infarction of the left anterior cingulate cortex and corpus callosum.

    Science.gov (United States)

    Suzuki, Tadashi; Itoh, Shouichi; Hayashi, Mototaka; Kouno, Masako; Takeda, Katsuhiko

    2009-10-01

    We report the case of a 69-year-old woman with cerebral infarction in the left anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a distinctive reading phenomenon, as well as ambient echolalia. Clinical features also included complex disorders such as visual groping, compulsive manipulation of tools, and callosal disconnection syndrome. She read words written on the cover of a book and repeated words emanating from unrelated conversations around her or from hospital announcements. The combination of these two features due to a focal lesion has never been reported previously. The supplementary motor area may control the execution of established subroutines according to external and internal inputs. Hyperlexia as well as the compulsive manipulation of tools could be interpreted as faulty inhibition of preexisting essentially intact motor subroutines by damage to the anterior cingulate cortex reciprocally interconnected with the supplementary motor area.

  9. 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...... in the adult. The mechanisms underlying the late effects of early exposure are not clear. To gain insight into the initial neurodevelopmental damage inflicted by PBDE-99, we investigated the short-term effects of PBDE-99 on protein expression in the developing cerebral cortex of neonatal mice...... are known to be cytoskeleton-related. Similar to previous findings in the striatum, we found elevated levels of the neuron growth-associated protein Gap43 in the cortex. In cultured cortical cells, a high concentration of PBDE-99 (30 microM) induced cell death without any apparent increase in caspase-3...

  10. Characterization of L-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer's disease and the normal.

    Science.gov (United States)

    Flynn, D D; Mash, D C

    1986-12-01

    Putative nicotine receptors in the human cerebral cortex were characterized with L-[3H]nicotine, L-[3H]Nicotine binding was enhanced by the addition of Ca2+ and abolished in the presence of Na3EDTA. Association and dissociation of the ligand were rapid at 25 degrees C with t1/2 values of 2 and 3 min, respectively. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 5.6 nM and a Hill coefficient of 1.05. There was no effect of postmortem interval on the density of binding sites assayed up to 24 h in rat frontoparietal cortex. Nicotine binding in human cortical samples was also unaltered by increasing sampling delay. In human cortical membranes, binding site density decreased with normal aging. Receptor affinity and concentration in samples of frontal cortex (Brodmann area 10) from patients with Alzheimer's disease were comparable to age-matched control values. Samples of infratemporal cortex (Brodmann area 38) from patients with Alzheimer's disease had a 50% reduction in the number of L-[3H]nicotine sites. Choline acetyltransferase activity was significantly decreased in both cortical areas. Enzyme activities in the temporal pole were reduced to 20% of control values. These data indicate that postsynaptic nicotine receptors are spared in the frontal cortex in Alzheimer's disease. In the infratemporal cortex, significant numbers of receptors remain despite the severe reduction in choline acetyltransferase activity. Replacement therapy directed at these sites may be warranted in Alzheimer's disease.

  11. Physiological activation of the human cerebral cortex during auditory perception and speech revealed by regional increases in cerebral blood flow

    DEFF Research Database (Denmark)

    Lassen, N A; Friberg, L

    1988-01-01

    by measuring regional cerebral blood flow CBF after intracarotid Xenon-133 injection are reviewed with emphasis on tests involving auditory perception and speech, and approach allowing to visualize Wernicke and Broca's areas and their contralateral homologues in vivo. The completely atraumatic tomographic CBF...

  12. Neuropil distribution in the cerebral cortex differs between humans and chimpanzees.

    Science.gov (United States)

    Spocter, Muhammad A; Hopkins, William D; Barks, Sarah K; Bianchi, Serena; Hehmeyer, Abigail E; Anderson, Sarah M; Stimpson, Cheryl D; Fobbs, Archibald J; Hof, Patrick R; Sherwood, Chet C

    2012-09-01

    Increased connectivity of high-order association regions in the neocortex has been proposed as a defining feature of human brain evolution. At present, however, there are limited comparative data to examine this claim fully. We tested the hypothesis that the distribution of neuropil across areas of the neocortex of humans differs from that of one of our closest living relatives, the common chimpanzee. The neuropil provides a proxy measure of total connectivity within a local region because it is composed mostly of dendrites, axons, and synapses. Using image analysis techniques, we quantified the neuropil fraction from both hemispheres in six cytoarchitectonically defined regions including frontopolar cortex (area 10), Broca's area (area 45), frontoinsular cortex (area FI), primary motor cortex (area 4), primary auditory cortex (area 41/42), and the planum temporale (area 22). Our results demonstrate that humans exhibit a unique distribution of neuropil in the neocortex compared to chimpanzees. In particular, the human frontopolar cortex and the frontoinsular cortex had a significantly higher neuropil fraction than the other areas. In chimpanzees these prefrontal regions did not display significantly more neuropil, but the primary auditory cortex had a lower neuropil fraction than other areas. Our results support the conclusion that enhanced connectivity in the prefrontal cortex accompanied the evolution of the human brain. These species differences in neuropil distribution may offer insight into the neural basis of human cognition, reflecting enhancement of the integrative capacity of the prefrontal cortex.

  13. A pattern formed by preferential orientation of tangential fibres in layer I of the rabbit's cerebral cortex.

    Science.gov (United States)

    Fleischhauer, K; Laube, A

    1977-12-01

    1. The tangential organization of layer I has been studied in frozen sections impregnated according to a modified Liesegang method and in Bodian impregnated paraffin sections cut tangentially to the dorsal surface of the rabbit's cerebral cortex. 2. It is shown that sublamina tangentialis of layer I contains a system of parallel nerve fibres forming a distinct pattern in the tangential plane. 3. This pattern has been reconstructed for a large region of the dorsal surface of the cerebral cortex including the striate areas as well as the peristriate, parietal and precentral agranular regions and parts of the retrosplenial area. 4. In most parts of the region investigated, the tangential fibres of layer I are oriented in an antero-medial to postero-lateral direction, forming an angle of about 50 degrees with the sagittal plane. 5. Deviations from this pattern are found in the furrows formed by the lateral sulcus and the frontal impression and also in the caudal part of the retrosplenial area. In these regions, which are characterized by comparatively steep changes of the cortical relief, the fibres course in a more sagittal direction.

  14. Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex.

    Science.gov (United States)

    Dean, Justin M; Fraser, Mhoyra; Shelling, Andrew N; Bennet, Laura; George, Sherly; Shaikh, Shamim; Scheepens, Arjan; Gunn, Alistair J

    2005-10-03

    This study examined the hypothesis that the high prevalence of white matter injury in premature infants is associated with increased expression of calcium-permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We characterized expression of subunits of the AMPA, and for reference, the N-methyl-d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in the ovine fetal white matter and cerebral cortex. There was a low expression of the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white matter both absolutely and relative to other AMPA subunits throughout gestation. In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with increasing gestation whereas protein expression increased. These findings suggest a vulnerability of subcortical white matter to AMPA receptor-mediated calcium toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA receptor-mediated glutamate toxicity contributes to brain damage in premature infants needs to be revised.

  15. Chemical interactions with pyramidal neurons in layer 5 of the cerebral cortex: control of pain and anxiety.

    Science.gov (United States)

    Adams, J D

    2009-01-01

    Pyramidal neurons in layer 5 of the cerebral cortex are involved in learning and memory and have complex connections with other neurons through a very large array of dendrites. These dendrites can switch between long term depression and long term potentiation depending on global summation of various inputs. The plasticity of the input into pyramidal neurons makes the neuronal output variable. Many interneurons in the cerebral cortex and distant neurons in other brain regions are involved in providing input to pyramidal neurons. All of these neurons and interneurons have neurotransmitters that act through receptors to provide input to pyramidal neurons. Serotonin is one of the important neurotransmitters involved with pyramidal neurons and has been implicated in psychosis, psychedelic states and what are called sacred dreams. This review will discuss the various chemicals and receptors that are important with pyramidal neurons including opioids, nicotine, scopolamine, psilocybin, LSD, mescaline, ergot alkaloids, salvinorin A, ergine and other compounds that interact with opioid, nicotinic, muscarinic and serotonergic receptors. The natural compounds provide clues to structure activity relationships with the receptors. It has been postulated that each receptor in the body has a natural agonist and antagonist, in addition to the normal neurotransmitters. It is common for natural antagonists and agonists to be peptides. Various possible peptide structures will be proposed for natural antagonists and agonists at each receptor. Natural antagonists and agonists may provide new ways to explore the functions of pyramidal neurons in normal health and pain management.

  16. 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.

  17. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    Science.gov (United States)

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  18. 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.

  19. Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

    Directory of Open Access Journals (Sweden)

    Valeska Lizzi Lagranha

    Full Text Available We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits, AMPA (GluR2 subunit and kainate (GluR6 subunit, as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT and glutaryl-CoA dehydrogenase deficient (Gchh-/- mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

  20. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, J.W.; Halonen, M.; Seaver, N.A.; Yamamura, H.I.

    1987-07-27

    Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting (TH)(-)quinuclidinyl benzilate or (TH)pirenzepine, the authors found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This results demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex. 20 references, 1 figure, 2 tables.

  1. THE EFFECT OF LIGUSTRAZINE ON NEUROGENESIS IN CORTEX AFTER FOCAL CEREBRAL ISCHEMIA IN RATS

    Institute of Scientific and Technical Information of China (English)

    邱芬; 刘勇; 张蓬勃; 康前雁; 田英芳; 陈新林; 赵建军; 祁存芳

    2006-01-01

    It has been demonstrated that there are neuralstemcells that can self-renewand differentiate intomultiple cell types[1-3]in central nervous system ofadult mammals.After cerebral ischemia,these cellscan proliferate,migrate,differentiate and partici-pate in the repair of ischemic cerebral injuries[4-6].Neural stemcells play a very i mportant role in alle-viating ischemic cerebral injuries and promotingfunctional recovery.Ligustrazine,an active ingre-dient of Ligustici,can help dilate blood vessels,i m-prove m...

  2. A comparison of the apoptotic effect of Delta(9)-tetrahydrocannabinol in the neonatal and adult rat cerebral cortex.

    Science.gov (United States)

    Downer, Eric J; Gowran, Aoife; Campbell, Veronica A

    2007-10-17

    The maternal use of cannabis during pregnancy results in a number of cognitive deficits in the offspring that persist into adulthood. The endocannabinoid system has a role to play in neurodevelopmental processes such as neurogenesis, migration and synaptogenesis. However, exposure to phytocannabinoids, such as Delta(9)-tetrahydrocannabinol, during gestation may interfere with these events to cause abnormal patterns of neuronal wiring and subsequent cognitive impairments. Aberrant cell death evoked by Delta(9)-tetrahydrocannabinol may also contribute to cognitive deficits and in cultured neurones Delta(9)-tetrahydrocannabinol induces apoptosis via the CB(1) cannabinoid receptor. In this study we report that Delta(9)-tetrahydrocannabinol (5-50 microM) activates the stress-activated protein kinase, c-jun N-terminal kinase, and the pro-apoptotic protease, caspase-3, in in vitro cerebral cortical slices obtained from the neonatal rat brain. The proclivity of Delta(9)-tetrahydrocannabinol to impact on these pro-apoptotic signalling molecules was not observed in in vitro cortical slices obtained from the adult rat brain. In vivo, subcutaneous administration of Delta(9)-tetrahydrocannabinol (1-30 mg/kg) activated c-jun N-terminal kinase, caspase-3 and cathepsin-D, and induced DNA fragmentation in the cerebral cortex of neonatal rats. In contrast, in vivo administration of Delta(9)-tetrahydrocannabinol to adult rats was not associated with the apoptotic pathway in the cerebral cortex. The data provide evidence which supports the hypothesis that the neonatal rat brain is more vulnerable to the neurotoxic influence of Delta(9)-tetrahydrocannabinol, suggesting that the cognitive deficits that are observed in humans exposed to marijuana during gestation may be due, in part, to abnormal engagement of the apoptotic cascade during brain development.

  3. Post-hypoxic and ischemic neuroprotection of BMP-7 in the cerebral cortex and caudate-putamen tissue of rat.

    Science.gov (United States)

    Luan, Liju; Yang, Xiaomei; Zhou, Changman; Wang, Ke; Qin, Lihua

    2015-03-01

    Previous reports have indicated that exogenous bone morphogenetic protein-7 (BMP-7) has a neuroprotective effect after cerebral ischemia injury and promotes motor function recovery, but the appropriate BMP-7 concentration and time course are unclear. Here, we assessed endogenous BMP-7 expression in hypoxia and ischemia-damaged brain tissues and investigated the effects of different BMP-7 concentrations in pre- and post-hypoxic primary rat neurons. The results showed that BMP-7 expression was significantly higher in the ischemic hemisphere. The expressions of BMP-7 and caspase-3 were localized in the cytoplasm of the primary cerebral cortical and caudate-putamen neurons 24h after hypoxia/reoxygenation. After BMP-7 treatment, the number of caspase-3 positive neurons began to decrease with increasing BMP-7 concentrations up to 80ng/ml, but not beyond. Although the numbers of caspase-3-positive neurons between pre- and post-hypoxia/reoxygenation were not significantly different, more dendrites were observed in the groups treated prior to hypoxia/reoxygenation. These results suggest that increased BMP-7 expression can be induced in the cerebral cortex and caudate-putamen both in vivo and in vitro in hypoxic-ischemic states. The neuroprotective mechanism of BMP-7 may include apoptosis suppression, and its effect was enhanced from 40 to 80ng/ml. Pre-hypoxic BMP-7 treatment may be useful to stimulate dendrite sprouting in non-injured neurons.

  4. Photobiomodulation with near infrared light mitigates Alzheimer's disease-related pathology in cerebral cortex - evidence from two transgenic mouse models.

    Science.gov (United States)

    Purushothuman, Sivaraman; Johnstone, Daniel M; Nandasena, Charith; Mitrofanis, John; Stone, Jonathan

    2014-01-01

    Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer's disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at an age when substantial pathology is already present in the cerebral cortex. We studied two mouse models with AD-related pathologies: the K369I tau transgenic model (K3), engineered to develop neurofibrillary tangles, and the APPswe/PSEN1dE9 transgenic model (APP/PS1), engineered to develop amyloid plaques. Mice were treated with NIr 20 times over a four-week period and histochemistry was used to quantify AD-related pathological hallmarks and other markers of cell damage in the neocortex and hippocampus. In the K3 mice, NIr treatment was associated with a reduction in hyperphosphorylated tau, neurofibrillary tangles and oxidative stress markers (4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine) to near wildtype levels in the neocortex and hippocampus, and with a restoration of expression of the mitochondrial marker cytochrome c oxidase in surviving neurons. In the APP/PS1 mice, NIr treatment was associated with a reduction in the size and number of amyloid-β plaques in the neocortex and hippocampus. Our results, in two transgenic mouse models, suggest that NIr may have potential as an effective, minimally-invasive intervention for mitigating, and even reversing, progressive cerebral degenerations.

  5. Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder.

    Science.gov (United States)

    Smiley, John F; Saito, Mariko; Bleiwas, Cynthia; Masiello, Kurt; Ardekani, Babak; Guilfoyle, David N; Gerum, Scott; Wilson, Donald A; Vadasz, Csaba

    2015-09-01

    Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD.

  6. The primary motor and premotor areas of the human cerebral cortex.

    Science.gov (United States)

    Chouinard, Philippe A; Paus, Tomás

    2006-04-01

    Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

  7. Mapping cortical thickness of the patients with unilateral end-stage open angle glaucoma on planar cerebral cortex maps.

    Directory of Open Access Journals (Sweden)

    Piotr Bogorodzki

    Full Text Available PURPOSE: To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision. METHODS: 14 patients with unilateral end-stage primary open angle glaucoma (POAG and 12 age-matched control individuals with no problems with vision were selected for the study based on detailed ophthalmic examination. For each participant 3D high-resolution structural brain T1-weighted magnetization prepared MR images were acquired on a 3.0 T scanner. Brain cortex thickness was estimated using the FreeSurfer image analysis environment. After warping of subjects' cortical surfaces to FreeSurfer common space, differences between POAG and control groups were inferred at the group analysis level with the General Linear Model. RESULTS: The analysis performed revealed local thinning in the visual cortex areas in the POAG group. Statistically significant differences form 600 mm2 clusters located in the Brodmann area BA19 in the left and right hemisphere. CONCLUSION: Unilateral vision loss due to end-stage neuropathy from POAG is associated with significant thinning of cortical areas employed in vision.

  8. Existence of vimentin and GFAP protein expressions as a result of 2-Methoxyethanol administration in cerebral cortex tissue of Swiss Webster mice (Mus musculus): an immunohistochemical analysis.

    Science.gov (United States)

    Irnidayanti, Yulia

    2014-07-01

    Une of the plastic-based materials widely used in the plastics industry in various countries is ester phthalate. This compound will be oxidized in the body into 2-methoxyethanol (2-ME). The effect of 2-ME on human health and environment depends on the number, duration and the frequency of exposure. Recently, the incidence of brain damage tends to increase. In the last decade, it has been widely reported the negative effects of chemical pollutants to the environment. The aim of this study were to know the existence of the expression of Vimentin and GFAP proteins caused by 2-ME on the histological structure of the cerebral cortex of mice fetal during the prenatal period on gestation day 14 (GD 14) and day 18 (GD 18). The 2-ME compound was injected intraperitoneally with a dose of 7.5 mmol kg(-1) of body weight at GD-10. The result showed that there is a change in existence Vimentin protein in the cerebral cortex fetal of treated mice at GD 14, which is very conspicuous. Meanwhile, a change in existence of GFAP protein in cerebral cortex fetal of treated mice at GD 14, have relatively no difference from controls and no impact on histological structure changes of the cerebral corteks at GD 14. The change in existence of Vimentin protein in the cerebral cortex fetal of treated mice at GD 14 have an impact on histological structure of the cerebral cortex of mice treated at GD 18. It is believed that the impact is due to the effects of 2-methoxyethanol.

  9. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Directory of Open Access Journals (Sweden)

    Mariane Wohlenberg

    2014-04-01

    Full Text Available In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4. The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract.

  10. 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.)

  11. Cl(-) conduction of GABAA receptor complex of synaptic membranes in the cortex of rats at the middle stage of chronic cerebral epileptization (pharmacological kindling).

    Science.gov (United States)

    Rebrov, I G; Karpova, M N; Andreev, A A; Klishina, N Yu; Kalinina, M V; Kusnetzova, L V

    2007-11-01

    Experiments on Wistar rats showed a decrease in basal and muscimol-stimulated 36Cl(-) entry into synaptoneurosomes isolated from the cerebral cortex during the middle stage of kindling (30 mg/kg pentylenetetrazole intraperitoneally for 14 days) characterized by the development of convulsions of higher (2 points) severity in comparison with the previous stage.

  12. 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 anteri

  13. 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.

  14. The dual network of GABAergic interneurons linked by both chemical and electrical synapses: a possible infrastructure of the cerebral cortex.

    Science.gov (United States)

    Fukuda, T; Kosaka, T

    2000-10-01

    To know the structural feature of individual nerve cells and of the network they form is essentially important for understanding how the brain works. We have recently shown that a certain subpopulation of hippocampal GABAergic neurons that contain a calcium-binding protein parvalbumin form the dual network connected by both chemical synapses and gap junctions. The mutual chemical synaptic contacts are formed between their axon terminals and somata whereas gap junctions are located between their dendrites. In this article, we demonstrate that the dual network of parvalbumin-containing GABAergic interneurons is not restricted to the hippocampus but found also in the neocortex and, therefore, appears to be a fundamental structure of the cerebral cortex, possibly having some relevance to the synchronized activities observed broadly in various cortical areas.

  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...... of neurovascular coupling after topical pretreatment with either inhibitor of CaN pathway (FK506), inhibitor of mPTP formation (NIM811) and combined inhibition of both pathways (FK506+NIM811 or cyclosporin A). A result indicating a potential new treatment aspect for disease states where CSD is known to be involved...

  16. NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar-bipolar transition.

    Science.gov (United States)

    Chen, Tianda; Wu, Qinwei; Zhang, Yang; Zhang, Dai

    2015-11-02

    Abnormalities during brain development are tightly linked several psychiatric disorders. Mutations in NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2) are responsible for schizophrenia, bipolar disorder and Parkinson׳s disease. However, the function of NDUFV2 during brain development remains unclear. Here we reported that ndufv2 is expressed in the developing cerebral cortex. In utero suppression of ndufv2 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. ndufv2 inhibition did not affect radial glia scaffold, progenitor cells or neurons survival. However, the loss of ndufv2 impairs neuronal multipolar-bipolar transition in vivo and polarization in vitro. Moreover, ndufv2 affected actin cytoskeleton and tubulin stabilization in cortical neurons. Overall, our findings establish a new NDUFV2 dependent mechanism underlying neuronal migration and psychiatric disorders.

  17. Preventive effects of dextromethorphan on methylmercury-induced glutamate dyshomeostasis and oxidative damage in rat cerebral cortex.

    Science.gov (United States)

    Feng, Shu; Xu, Zhaofa; Liu, Wei; Li, Yuehui; Deng, Yu; Xu, Bin

    2014-06-01

    Methylmercury (MeHg) is a well-known environmental pollutant leading to neurotoxicant associated with aberrant central nervous system (CNS) functions, but its toxic mechanisms have not yet been fully recognized. In the present study, we tested the hypothesis that MeHg induces neuronal injury via glutamate (Glu) dyshomeostasis and oxidative damage mechanisms and that these effects are attenuated by dextromethorphan (DM), a low-affinity and noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist. Seventy-two rats were randomly divided into four groups of 18 animals in each group: control group, MeHg-treated group (4 and 12 μmol/kg), and DM-pretreated group. After the 4-week treatment, we observed that the administration of MeHg at a dose of 12 μmol/kg significantly increased in total mercury (Hg) levels, disrupted Glu metabolism, overexcited NMDARs, and led to intracellular calcium overload in the cerebral cortex. We also found that MeHg reduced nonenzymatic and enzymatic antioxidants, enhanced neurocyte apoptosis, induced reactive oxygen species (ROS), and caused lipid, protein, and DNA peroxidative damage in the cerebral cortex. Moreover, glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) appeared to be inhibited by MeHg exposure. These alterations were significantly prevented by the pretreatment with DM at a dose of 13.5 μmol/kg. In conclusion, these findings strongly implicate that DM has potential to protect the brain from Glu dyshomeostasis and oxidative damage resulting from MeHg-induced neurotoxicity in rat.

  18. Rabbit forebrain cholinergic system: morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus.

    Science.gov (United States)

    Varga, Csaba; Härtig, Wolfgang; Grosche, Jens; Keijser, Jan; Luiten, Paul G M; Seeger, Johannes; Brauer, Kurt; Harkany, Tibor

    2003-06-09

    Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output pathways are still awaited. Therefore, we performed quantitative choline acetyltransferase (ChAT) immunocytochemistry to localize major cholinergic nuclei and to determine the number of respective cholinergic neurons in the rabbit forebrain. The density of ChAT-immunoreactive terminals in layer V of distinct neocortical territories and in hippocampal subfields was also measured. Another cholinergic marker, the low-affinity neurotrophin receptor (p75(NTR)), was also employed to identify subsets of cholinergic neurons. Double-immunofluorescence labeling of ChAT and p75(NTR), calbindin D-28k (CB), parvalbumin, calretinin, neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase, or substance P was used to elucidate the neuroanatomical borders of cholinergic nuclei and to analyze the neurochemical complexity of cholinergic cell populations. Cholinergic projection neurons with heterogeneous densities were found in the medial septum, vertical and horizontal diagonal bands of Broca, ventral pallidum, and magnocellular nucleus basalis (MBN)/substantia innominata (SI) complex; cholinergic interneurons were observed in the caudate nucleus, putamen, accumbens nucleus, and olfactory tubercule, whereas the globus pallidus was devoid of cholinergic nerve cells. Cholinergic interneurons were frequently present in the hippocampus and to a lesser extent in cerebral cortex. Cholinergic projection neurons, except those localized in SI, abundantly expressed p75(NTR), and a subset of cholinergic neurons in posterior MBN was immunoreactive for CB and nNOS. A strict laminar distribution pattern of cholinergic terminals was recorded both in the cerebral cortex and in CA1-CA3 and dentate gyrus

  19. Attenuation of γ-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to β-cypermethrin.

    Science.gov (United States)

    Han, Y; Cao, D; Li, X; Zhang, R; Yu, F; Ren, Y; An, L

    2014-03-01

    The current study investigated the γ-aminobutyric acid (GABA) levels and GABA metabolic enzymes (GABA transaminase (GABA(T)) and glutamate decarboxylase (GAD)) activities at 2 and 4 h after treatment, using a high-performance liquid chromatography with ultraviolet detectors and colorimetric assay, in the cerebral cortex of mice treated with 20, 40 or 80 mg/kg β-cypermethrin by a single oral gavage, with corn oil as vehicle control. In addition, GABA protein (4 h after treatment), GABA(T) protein (2 h after treatment) and GABA receptors messenger RNA (mRNA) expression were detected by immunohistochemistry, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction, respectively. β-Cypermethrin (80 mg/kg) significantly increased GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. Also, GABA immunohistochemistry results suggested that the number of positive granules was increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg β-cypermethrin when compared with the control. Furthermore, the results also showed that GABA(T) activity detected was significantly decreased in the cerebral cortex of mice 2 h after β-cypermethrin administration (40 or 80 mg/kg). No significant changes were found in GAD activity, or the expression of GABA(T) protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg β-cypermethrin caused a significant decrease, compared with the vehicle control, in GABAA receptors mRNA expression 4 h after administration. These results suggested that attenuated GABA(T) activity induced by β-cypermethrin contributed to increased GABA levels in the mouse brain. The downregulated GABAA receptors mRNA expression is most likely a downstream event.

  20. Focal increase of blood flow in the cerebral cortex of man during vestibular stimulation

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1985-01-01

    This study is an attempt to reveal projection areas for vestibular afferents to the human brain. Changes in regional cerebral blood flow (rCBF) were measured over 254 cortical regions during caloric vestibular stimulation with warm water (44 degrees C). rCBF was measured when the external auditor...... stimulation that gives rise to the associated conscious vestibular sensation of vertigo....

  1. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex.

    Science.gov (United States)

    Ohshima, Toshio; Hirasawa, Motoyuki; Tabata, Hidenori; Mutoh, Tetsuji; Adachi, Tomoko; Suzuki, Hiromi; Saruta, Keiko; Iwasato, Takuji; Itohara, Shigeyoshi; Hashimoto, Mistuhiro; Nakajima, Kazunori; Ogawa, Masaharu; Kulkarni, Ashok B; Mikoshiba, Katsuhiko

    2007-06-01

    The mammalian cerebral cortex consists of six layers that are generated via coordinated neuronal migration during the embryonic period. Recent studies identified specific phases of radial migration of cortical neurons. After the final division, neurons transform from a multipolar to a bipolar shape within the subventricular zone-intermediate zone (SVZ-IZ) and then migrate along radial glial fibres. Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal migration defects. When we introduced GFP into migrating neurons at E14.5 by in utero electroporation, we observed migrating neurons in wild-type but not in Cdk5(-/-) embryos after 3-4 days. Introduction of the dominant-negative form of Cdk5 into the wild-type migrating neurons confirmed specific impairment of the multipolar-to-bipolar transition within the SVZ-IZ in a cell-autonomous manner. Cortex-specific Cdk5 conditional knockout mice showed inverted layering of the cerebral cortex and the layer V and callosal neurons, but not layer VI neurons, had severely impaired dendritic morphology. The amount of the dendritic protein Map2 was decreased in the cerebral cortex of Cdk5-deficient mice, and the axonal trajectory of cortical neurons within the cortex was also abnormal. These results indicate that Cdk5 is required for proper multipolar-to-bipolar transition, and a deficiency of Cdk5 results in abnormal morphology of pyramidal neurons. In addition, proper radial neuronal migration generates an inside-out pattern of cerebral cortex formation and normal axonal trajectories of cortical pyramidal neurons.

  2. Effects of melatonin on learning abilities, cholinergic fibers and nitric oxide synthase expression in rat cerebral cortex

    Institute of Scientific and Technical Information of China (English)

    Bin Xu; Junpao Chen; Hailing Zhao

    2006-01-01

    BACKGROUND: Melatonin is a kind of hormones derived from pineal gland. Recent researches demonstrate that melatonin is characterized by anti-oxidation, anti-senility and destroying free radicals. While, effect and pathogenesis of pineal gland on learning ability should be further studied.OBJ ECTIVE: To investigate the effects of pinealectomy on learning abiliy, distribution of cholinesterase and expression of neuronal nitric oxide synthase (nNOS) in cerebral cortex of rats and probe into the effect of melatonin on learning ability, central cholinergic system and nNOS expression.DESIGN: Randomized grouping design and animal study.SETTING: Department of Neurology, the 187 Hospital of Chinese PLA.MATERIALS: A total of 12 male SD rats, of normal learning ability testing with Y-tape maze, of clean grade,weighing 190-210 g, aged 6 weeks, were selected in this study.METHODS: The experiment was carried out in the Department of Neurology, Zhujiang Hospital from July 1997to June 2000. All SD rats were divided into experimental group (n =6,pinealectomy) and control group (n =6, sham operation). Seven days later, rats in both two groups were continuously fed for 33 days. ①Learning ability test: The learning ability of rats was tested by trisection Y-type maze and figured as attempting times. ②Expression of acetylcholinesterase (AchE) was detected by enzyme histochemistry and nNOS was measured by SABC method. ③ Quantitative analysis of AchE fibers: AchE fibers density in unit area (surface density)was surveyed with Leica Diaplan microscope and Leica Quantimet 500+ image analytic apparatus and quantitative parameter was set up for AchE fibers covering density (μm2) per 374 693.656 μm2, moreover, the AchE fibers density was measured in Ⅱ -Ⅳ layers of motor and somatosensory cortex (showing three layers per field of vision at one time), in radiative, lacunaria and molecular layers of CA1, CA2 and CA3 areas, and in lamina multiforms of dentate gyrus. Three tissue slices

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

    NARCIS (Netherlands)

    Turk, Elise; Scholtens, Lianne H.; van den Heuvel, Martijn P.|info:eu-repo/dai/nl/304820466

    2016-01-01

    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 cortica

  4. Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

    Directory of Open Access Journals (Sweden)

    Andrew Pollock

    2014-05-01

    Full Text Available Proper growth of the mammalian cerebral cortex is crucial for normal brain functions and is controlled by precise gene-expression regulation. Here, we show that microRNA-7 (miR-7 is highly expressed in cortical neural progenitors and describe miR-7 sponge transgenic mice in which miR-7-silencing activity is specifically knocked down in the embryonic cortex. Blocking miR-7 function causes microcephaly-like brain defects due to reduced intermediate progenitor (IP production and apoptosis. Upregulation of miR-7 target genes, including those implicated in the p53 pathway, such as Ak1 and Cdkn1a (p21, is responsible for abnormalities in neural progenitors. Furthermore, ectopic expression of Ak1 or p21 and specific blockade of miR-7 binding sites in target genes using protectors in vivo induce similarly reduced IP production. Using conditional miRNA sponge transgenic approaches, we uncovered an unexpected role for miR-7 in cortical growth through its interactions with genes in the p53 pathway.

  5. An enhanced role and expanded developmental origins for gamma-aminobutyric acidergic interneurons in the human cerebral cortex.

    Science.gov (United States)

    Clowry, Gavin J

    2015-10-01

    Human beings have considerably expanded cognitive abilities compared with all other species and they also have a relatively larger cerebral cortex compared with their body size. But is a bigger brain the only reason for higher cognition or have other features evolved in parallel? Humans have more and different types of GABAergic interneurons, found in different places, than our model species. Studies are beginning to show differences in function. Is this expanded repertoire of functional types matched by an evolution of their developmental origins? Recent studies support the idea that generation of interneurons in the ventral telencephalon may be more complicated in primates, which have evolved a large and complex outer subventricular zone in the ganglionic eminences. In addition, proportionally more interneurons appear to be produced in the caudal ganglionic eminence, the majority of which populate the superficial layers of the cortex. Whether or not the cortical proliferative zones are a source of interneurogenesis, and to what extent and of what significance, is a contentious issue. As there is growing evidence that conditions such as autism, schizophrenia and congenital epilepsy may have developmental origins in the failure of interneuron production and migration, it is important we understand fully the similarities and differences between human development and our animal models.

  6. 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.

  7. Role of Late Maternal Thyroid Hormones in Cerebral Cortex Development: An Experimental Model for Human Prematurity

    OpenAIRE

    Berbel, P.; Navarro, D.; Ausó, E.; Varea, E; Rodríguez, A E; Ballesta, J. J.; Salinas, M; Flores, E; Faura, C. C.; Morreale de Escobar, G

    2009-01-01

    Hypothyroxinemia affects 35–50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats...

  8. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny.

    Science.gov (United States)

    Lavado-Autric, Rosalía; Ausó, Eva; García-Velasco, José Victor; Arufe, María del Carmen; Escobar del Rey, Francisco; Berbel, Pere; Morreale de Escobar, Gabriella

    2003-04-01

    Epidemiological studies from both iodine-sufficient and -deficient human populations strongly suggest that early maternal hypothyroxinemia (i.e., low circulating free thyroxine before onset of fetal thyroid function at midgestation) increases the risk of neurodevelopmental deficits of the fetus, whether or not the mother is clinically hypothyroid. Rat dams on a low iodine intake are hypothyroxinemic without being clinically hypothyroid because, as occurs in pregnant women, their circulating 3,5,3'-triiodothyronine level is usually normal. We studied cell migration and cytoarchitecture in the somatosensory cortex and hippocampus of the 40-day-old progeny of the iodine-deficient dams and found a significant proportion of cells at locations that were aberrant or inappropriate with respect to their birth date. Most of these cells were neurons, as assessed by single- and double-label immunostaining. The cytoarchitecture of the somatosensory cortex and hippocampus was also affected, layering was blurred, and, in the cortex, normal barrels were not formed. We believe that this is the first direct evidence of an alteration in fetal brain histogenesis and cytoarchitecture that could only be related to early maternal hypothyroxinemia. This condition may be 150-200 times more common than congenital hypothyroidism and ought to be prevented both by mass screening of free thyroxine in early pregnancy and by early iodine supplementation to avoid iodine deficiency, however mild.

  9. 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.

  10. Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.

    Science.gov (United States)

    Hanaya, R; Hosoyama, H; Sugata, S; Tokudome, M; Hirano, H; Tokimura, H; Kurisu, K; Serikawa, T; Sasa, M; Arita, K

    2012-09-27

    The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

  11. 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.

  12. Dynamics of spontaneous activity in the cerebral cortex across brain states

    OpenAIRE

    Jercog, Daniel Alejandro

    2013-01-01

    [spa] La actividad espontánea en la corteza cerebral cambia en diferentes estados cerebrales. Durante estados desincronizados (e.g. estado de vigilia, sueño MOR), las poblaciones de neuronas en los potenciales de acción en una manera aparentemente estocástica y no correlacionada. Por el contrario, durante estados sincronizados (e.g. sueño de ondas lentas, anestesia) las neuronas corticales muestran la alternancia entre periodos de reposo (DOWN) y los períodos de actividad (UP) de manera coher...

  13. [Effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water].

    Science.gov (United States)

    Xiuwen, Yang; Hongchen, Liu; Ke, Li; Zhen, Jin; Gang, Liu

    2014-12-01

    We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water. Six male and female subjects were subjected to whole-brain fMRI during the phasic delivery of non-noxious hot (23 °C) and no- xious cold (4 °C) water intraoral stimulation. A block-design blood oxygenation level-dependent fMRI scan covering the entire brain was also carried out. The activated cortical areas were as follows: left pre-/post-central gyrus, insula/operculum, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), midbrain red nucleus, and thalamus. The activated cortical areas under cold condition were as follows: left occipital lobe, premotor cortex/Brodmann area (BA) 6, right motor language area BA44, lingual gyrus, parietal lobule (BA7, 40), and primary somatosensory cortex S I. Comparisons of the regional cerebral blood flow response magnitude were made among stereotactically concordant brain regions that showed significant responses under the two conditions of this study. Compared with non-noxious warmth, more regions were activated in noxious coldness, and the magnitude of activation in areas produced after non-noxious warm stimulation significantly increased. However, ACC only significantly increased the magnitude of activation under noxious coldness stimulation. Results suggested that a similar network of regions was activated common to the perception of pain and no-pain produced by either non-noxious warmth or noxious coldness stimulation. Non-noxious warmth also activated more brain regions and significantly increased the response magnitude of cerebral-cortex activation compared with noxious coldness. Noxious coldness stimulation further significantly increased the magnitude of activation in ACC areas compared with noxious warmth.

  14. An analysis of von Economo neurons in the cerebral cortex of cetaceans, artiodactyls, and perissodactyls.

    Science.gov (United States)

    Raghanti, Mary Ann; Spurlock, Linda B; Treichler, F Robert; Weigel, Sara E; Stimmelmayr, Raphaela; Butti, Camilla; Thewissen, J G M Hans; Hof, Patrick R

    2015-07-01

    Von Economo neurons (VENs) are specialized projection neurons with a characteristic spindle-shaped soma and thick basal and apical dendrites. VENs have been described in restricted cortical regions, with their most frequent appearance in layers III and V of the anterior cingulate cortex, anterior insula, and frontopolar cortex of humans, great apes, macaque monkeys, elephants, and some cetaceans. Recently, a ubiquitous distribution of VENs was reported in various cortical areas in the pygmy hippopotamus, one of the closest living relatives of cetaceans. That finding suggested that VENs might not be unique to only a few species that possess enlarged brains. In the present analysis, we assessed the phylogenetic distribution of VENs within species representative of the superordinal clade that includes cetartiodactyls and perissodactyls, as well as afrotherians. In addition, the distribution of fork cells that are often found in close proximity to VENs was also assessed. Nissl-stained sections from the frontal pole, anterior cingulate cortex, anterior insula, and occipital pole of bowhead whale, cow, sheep, deer, horse, pig, rock hyrax, and human were examined using stereologic methods to quantify VENs and fork cells within layer V of all four cortical regions. VENs and fork cells were found in each of the species examined here with species-specific differences in distributions and densities. The present results demonstrated that VENs and fork cells were not restricted to highly encephalized or socially complex species, and their repeated emergence among distantly related species seems to represent convergent evolution of specialized pyramidal neurons. The widespread phylogenetic presence of VENs and fork cells indicates that these neuron morphologies readily emerged in response to selective forces,whose variety and nature are yet to be identified.

  15. 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.)

  16. Does the cerebral cortex exploit high dimensional, non-linear dynamics for information processing?

    Directory of Open Access Journals (Sweden)

    Wolf Singer

    2016-09-01

    Full Text Available The discovery of stimulus induced synchronisation in the visual cortex suggested the possibility that the relations among low-level stimulus features are encoded by the temporal relationship between neuronal discharges. In this framework, temporal coherence is considered a signature of perceptual grouping. This insight triggered a large number of experimental studies which sought to investigate the relationship between temporal coordination and cognitive functions. While some core predictions derived from the initial hypothesis were confirmed, these studies, also revealed a rich dynamical landscape beyond simple coherence whose role in signal processing is still poorly understood. In this paper a framework is presented which establishes links between the various manifestations of cortical dynamics by assigning specific coding functions to low dimensional dynamic features such as synchronized oscillations and phase shifts on the one hand and high dimensional non-linear, non-stationary dynamics on the other. The data serving as basis for this synthetic approach have been obtained with chronic multisite recordings from the visual cortex of anesthetized cats and from monkeys trained to solve cognitive tasks. It is proposed that the low dimensional dynamics characterized by synchronized oscillations and large-scale correlations are sub-states that represent the results of computations performed in the high dimensional state space provided by recurrently coupled networks.

  17. Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity

    Science.gov (United States)

    Richner, Thomas J.; Thongpang, Sanitta; Brodnick, Sarah K.; Schendel, Amelia A.; Falk, Ryan W.; Krugner-Higby, Lisa A.; Pashaie, Ramin; Williams, Justin C.

    2014-02-01

    Objective. Spatial localization of neural activity from within the brain with electrocorticography (ECoG) and electroencephalography remains a challenge in clinical and research settings, and while microfabricated ECoG (micro-ECoG) array technology continues to improve, complementary methods to simultaneously modulate cortical activity while recording are needed. Approach. We developed a neural interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays fabricated on a transparent polymer. This approach enabled us to directly modulate neural activity at known locations around micro-ECoG arrays in mice expressing Channelrhodopsin-2. We applied photostimuli varying in time, space and frequency to the cortical surface, and we targeted multiple depths within the cortex using an optical fiber while recording micro-ECoG signals. Main results. Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the entire cortical window, while focally applied photostimuli evoked spatially localized micro-ECoG potentials. Two simultaneously applied focal stimuli could be separated, depending on the distance between them. Photostimuli applied within the cortex with an optical fiber evoked more complex micro-ECoG potentials with multiple positive and negative peaks whose relative amplitudes depended on the depth of the fiber. Significance. Optogenetic ECoG has potential applications in the study of epilepsy, cortical dynamics, and neuroprostheses.

  18. OASIS regulates chondroitin 6-O-sulfotransferase 1 gene transcription in the injured adult mouse cerebral cortex.

    Science.gov (United States)

    Okuda, Hiroaki; Tatsumi, Kouko; Horii-Hayashi, Noriko; Morita, Shoko; Okuda-Yamamoto, Aya; Imaizumi, Kazunori; Wanaka, Akio

    2014-09-01

    Old astrocyte specifically induced substance (OASIS), a basic leucine zipper transcription factor of the cAMP response element binding/Activating transcription factor family, is induced in reactive astrocytes in vivo and has important roles in quality control of protein synthesis at the endoplasmic reticulum. Reactive astrocytes produce a non-permissive environment for regenerating axons by up-regulating chondroitin sulfate proteoglycans (CSPGs). In this study, we focus on the potential role of OASIS in CSPG production in the adult mouse cerebral cortex. CS-C immunoreactivity, which represents chondroitin sulfate moieties, was significantly attenuated in the stab-injured cortices of OASIS knockout mice compared to those of wild-type mice. We next examined expression of the CSPG-synthesizing enzymes and core proteins of CSPGs in the stab-injured cortices of OASIS knockout and wild-type mice. The levels of chondroitin 6-O-sulfotransferase 1 (C6ST1, one of the major enzymes involved in sulfation of CSPGs) mRNA and protein increased after cortical stab injury of wild-type, but not of OASIS knockout, mice. A C-terminal deletion mutant OASIS over-expressed in rat C6 glioma cells increased C6ST1 transcription by interacting with the first intron region. Neurite outgrowth of cultured hippocampal neurons was inhibited on culture dishes coated with membrane fractions of epidermal growth factor-treated astrocytes derived from wild type but not from OASIS knockout mice. These results suggest that OASIS regulates the transcription of C6ST1 and thereby promotes CSPG sulfation in astrocytes. Through these mechanisms, OASIS may modulate axonal regeneration in the injured cerebral cortex. OASIS, an ER stress-responsive CREB/ATF family member, is up-regulated in the reactive astrocytes of the injured brain. We found that the up-regulated OASIS is involved in the transcriptional regulation of C6ST1 gene, which promotes chondroitin sulfate proteoglycan (CSPG) sulfation. We conclude

  19. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    Science.gov (United States)

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  20. Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Audet, M.A.; Doucet, G.; Oleskevich, S.; Descarries, L.

    1988-08-15

    The regional and laminar distribution of the noradrenaline (NA) innervation in the adult rat cerebral cortex was quantified in radioautographs of semithin sections from whole hemisphere slices incubated with tritiated catecholamines and a monoamine oxidase inhibitor. Uptake-labeled axonal varicosities (aggregates of silver grains) were counted with the help of a computerized image analyzer in seven cytoarchitectonic areas of the rostral half of the cortex: Cg3, rostral AID, Cg2, Fr1, Par1, caudal AID, and Pir (prepiriform) according to Zilles's nomenclature. Both dopamine (DA) and NA terminals were detected after incubation with (3H)DA and citalopram or with (3H)NA alone. In the presence of desipramine (DMI), DA terminals alone were demonstrated; the number of NA terminals was then obtained by subtraction from counts in adjacent slices incubated with or without DMI. These counts suggested that DA and NA varicosities were fully visualized only after labeling with their respective tritiated amine. Similar numbers of labeled NA varicosities as inferred after (3H)NA incubation with or without DMI were observed after (3H)NA incubation in the presence of benztropine (BZ). This indicated that NA terminals were then maximally detected to the exclusion of the DA ones, and the latter approach was adopted for the acquisition of normative data. Since the average diameter of the labeled NA varicosities was known from earlier measurements in electron microscope radioautographs, the initial counts of labeled sites/mm2 of histological section could be expressed as numbers of varicosities/mm3 of tissue following a double correction for incomplete detection at the chosen duration of radioautographic exposure and section thickness.

  1. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons.

    Directory of Open Access Journals (Sweden)

    Kimberly D Siegmund

    Full Text Available The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5' CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts--defined by chronic neurodegeneration (Alzheimer's or lack thereof (schizophrenia--were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase.

  2. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    Science.gov (United States)

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice.

  3. 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.

  4. Role of mitochondrial calcium uniporter in regulating mitochondrial fission in the cerebral cortexes of living rats.

    Science.gov (United States)

    Liang, Nan; Wang, Peng; Wang, Shilei; Li, Shuhong; Li, Yu; Wang, Jinying; Wang, Min

    2014-06-01

    The mitochondrial calcium uniporter (MCU) transports Ca2+ from the cytoplasm to the mitochondrial matrix and thus maintains Ca2+ homeostasis. Previous studies have reported that inhibition of MCU by ruthenium red (RR) protects the brain from ischemia/reperfusion (I/R) injury and that mitochondrial fission plays an important role in I/R injury. However, it is still not known whether MCU affects mitochondrial fission. In the present study, treatment with RR was found to decrease the concentration of free calcium in the mitochondria, calcineurin enzyme activity and dynamin-related protein 1 expression, and treatment with spermine was found to have the opposite effect in organisms subjected to occlusion of the middle cerebral artery lasting 2 h followed by 24 h reperfusion. These results indicate that MCU may be related to mitochondrial fission via modulating mitochondrial Ca2+ uptake and this relationship between MCU and mitochondrial fission may protect the brain from I/R injury.

  5. Monosynaptic functional connectivity in cerebral cortex during wakefulness and under graded levels of anesthesia

    Directory of Open Access Journals (Sweden)

    Jeannette A Vizuete

    2012-10-01

    Full Text Available The balance between excitation and inhibition is considered to be of significant importance for neural computation and cognitive function. Excitatory and inhibitory functional connectivity in intact cortical neuronal networks in wakefulness and graded levels of anesthesia has not been systematically investigated. We compared monosynaptic excitatory and inhibitory spike transmission probabilities using pairwise cross-correlogram analysis. Spikes were measured at 64 sites in the visual cortex of rats with chronically implanted microelectrode arrays during wakefulness and three levels of anesthesia produced by desflurane. Anesthesia decreased the number of active units, the number of functional connections, and the strength of excitatory connections. Connection probability (number of connections per number of active unit pairs was unaffected until the deepest anesthesia level, at which a significant increase in the excitatory to inhibitory ratio of connection probabilities was observed. The results suggest that the excitatory-inhibitory balance is altered at an anesthetic depth associated with unconsciousness.

  6. Elevation of 4-hydroxynonenal and malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-bromopropane.

    Science.gov (United States)

    Zhong, Zhixia; Zeng, Tao; Xie, Keqin; Zhang, Cuili; Chen, Jingjing; Bi, Ye; Zhao, Xiulan

    2013-04-05

    1-Bromopropane (1-BP), an alternative to ozone-depleting solvents (ODS), exhibits central nervous system (CNS) toxicity in animals and humans. This study was designed to relate CNS damage by Morris water maze (MWM) test and oxidative stress to 1-BP exposure in the rat. Male Wistar rats were randomly divided into 4 groups (n=10), and treated with 0, 200, 400 and 800 mg/kgbw 1-BP for consecutive 12 days, respectively. From day 8 to day 12 of the experiment, MWM test was employed to assess the cognitive function of rats. The cerebral cortex of rats was obtained immediately following the 24h after MWM test conclusion. Glutathione (GSH), oxidized glutathione (GSSG) and total thiol (total-SH) content, GSH reductase (GR) and GSH peroxidase (GSH-Px) activities, malondialdehyde (MDA) level, as well as 4-hydroxynonenal (4-HNE) and MDA modified proteins in homogenates of cerebral cortex were measured. The obtained results showed that 1-BP led to cognitive dysfunction of rats, which was evidenced by delayed escape latency time and swimming distances in MWM performance. GSH and total-SH content, GSH/GSSG ratio, GR activity significantly decreased in cerebral cortex of rats, coupling with the increase of MDA level. 4-HNE and MDA modified protein levels obviously elevated after 1-BP exposure. GSH-Px activities in cerebral cortex of rats also increased. These data suggested that 1-BP resulted in enhanced lipid peroxidation of brain, which might play an important role in CNS damage induced by 1-BP.

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

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    Pedro Furtado De Mattos Ribeiro

    2014-04-01

    Full Text Available 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 Laurasitheria. 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

  8. Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice.

    Science.gov (United States)

    Temp, Fernanda Rossatto; Marafiga, Joseane Righes; Milanesi, Laura Hautrive; Duarte, Thiago; Rambo, Leonardo Magno; Pillat, Micheli Mainardi; Mello, Carlos Fernando

    2017-09-05

    Seizures increase prostaglandin and cytokine levels in the brain. However, it remains to be determined whether cyclooxygenase-2 (COX-2) derived metabolites play a role in seizure-induced cytokine increase in the brain and whether anticonvulsant activity is shared by all COX-2 inhibitors. In this study we investigated whether three different COX-2 inhibitors alter pentylenetetrazol (PTZ)-induced seizures and increase of interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex of mice. Adult male albino Swiss mice received nimesulide, celecoxib or etoricoxib (0.2, 2 or 20mg/kg in 0.1% carboxymethylcellulose (CMC) in 5% Tween 80, p.o.). Sixty minutes thereafter the animals were injected with PTZ (50mg/kg, i.p.) and the latency to myoclonic jerks and to generalized tonic-clonic seizures were recorded. Twenty minutes after PTZ injection animals were killed and cytokine levels were measured. PTZ increased cytokine levels in the cerebral cortex and hippocampus. While celecoxib and nimesulide attenuated PTZ -induced increase of proinflammatory cytokines in the cerebral cortex, etoricoxib did not. Nimesulide was the only COX-2 inhibitors that attenuated PTZ-induced seizures. This effect coincided with an increase of IL-10 levels in the cerebral cortex and hippocampus, constituting circumstantial evidence that IL-10 increase may be involved in the anticonvulsant effect of nimesulide. Copyright © 2017. Published by Elsevier B.V.

  9. Effects of Chloroquine on GFAP, PCNA and Cyclin D1 in Hippocampus and Cerebral Cortex of Rats with Seizures Induced by Pentylenetetrazole

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuhua; ZHU Changgeng; LIU Qingying; WANG Wei

    2005-01-01

    The effects of chloroquine on glial fibrillary acidic protein (GFAP), proliferation cell nuclear antigen (PCNA) and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole (PTZ) were observed in the present study. Forty-eight male adult Sprague-Dawley (SD) rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram (EEG) were observed and recor ded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group (Ⅳ-Ⅴ degree), and slight seizure activity ( Ⅰ - Ⅲ degree) in the chloroquine intervening group (P<0. 05). EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low-amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group (P <0.05 and P<0.01, respectively). No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups (P>0.05). The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups (P< 0.05). Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.

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

    OpenAIRE

    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 cortic...

  11. 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

    OpenAIRE

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

    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 choc...

  12. The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation

    OpenAIRE

    Chan, S.Y.; Martín-Santos, A; Loubière, L S; González, A. M.; Stieger, B.; LOGAN, A.; McCabe, C. J.; Franklyn, J.A.; Kilby, M. D.

    2011-01-01

    Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7–20 weeks gestation) and during retinoic acid induced neurodifferentiation of t...

  13. Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission.

    OpenAIRE

    Mrzljak, L; Levey, A I; Goldman-Rakic, P S

    1993-01-01

    Muscarinic m1 receptors traditionally are considered to be postsynaptic to cholinergic fibers, while m2 receptors are largely presynaptic receptors associated with axons. We have examined the distribution of these receptor proteins in the monkey cerebral cortex and obtained results that are at odds with this expectation. Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are prominently ...

  14. The plasma membrane redox system is impaired by amyloid β-peptide and in the hippocampus and cerebral cortex of 3xTgAD mice

    OpenAIRE

    Hyun, Dong-Hoon; Mughal, Mohamed R.; Yang, Hyunwon; Lee, Ji Hyun; Ko, Eun Joo; Hunt, Nicole D.; de Cabo, Rafael; Mattson, Mark P.

    2010-01-01

    Membrane-associated oxidative stress has been implicated in the synaptic dysfunction and neuronal degeneration that occurs in Alzheimer’s disease (AD), but the underlying mechanisms are unknown. Enzymes of the plasma membrane redox system (PMRS) provide electrons for energy metabolism and recycling of antioxidants. Here, we show that activities of several PMRS enzymes are selectively decreased in plasma membranes from the hippocampus and cerebral cortex of 3xTgAD mice, an animal model of AD. ...

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

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    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

  16. Expression of estrogen receptor (ER) -α and -β transcripts in the neonatal and adult rat cerebral cortex, cerebellum, and olfactory bulb

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In the present study expression of estrogen receptor subtype -α (ERα) and -β (ERβ) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1~ 3-days-old) and adult (250~350g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERα transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERα was present in the adult cerebral cortex. No significant difference in ERβ transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERα expression was significantly weaker than ERβ. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERα transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERα/ERβ transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.

  17. Creatine and pyruvate prevent the alterations caused by tyrosine on parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex of Wistar rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Bonorino, Narielle Ferner; Costa, Bruna May Lopes; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2015-01-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II. In this disease caused by tyrosine aminotransferase deficiency, eyes, skin, and central nervous system disturbances are found. In the present study, we investigated the chronic effect of tyrosine methyl ester (TME) and/or creatine plus pyruvate on some parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex homogenates of 21-day-old Wistar. Chronic administration of TME induced oxidative stress and altered the activities of adenylate kinase and mitochondrial and cytosolic creatine kinase. Total sulfhydryls content, GSH content, and GPx activity were significantly diminished, while DCFH oxidation, TBARS content, and SOD activity were significantly enhanced by TME. On the other hand, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions but enhanced AK activity. In contrast, TME did not affect the carbonyl content and PK activity in cerebral cortex of rats. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by TME administration on the oxidative stress and the enzymes of phosphoryltransfer network, except in mitochondrial CK, AK, and SOD activities. These results indicate that chronic administration of TME may stimulate oxidative stress and alter the enzymes of phosphoryltransfer network in cerebral cortex of rats. In case this also occurs in the patients affected by these disorders, it may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias, and creatine and pyruvate supplementation could be beneficial to the patients.

  18. MicroRNA function is required for neurite outgrowth of mature neurons in the mouse postnatal cerebral cortex

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    Janet eHong

    2013-09-01

    Full Text Available The structure of the postnatal mammalian cerebral cortex is an assembly of numerous mature neurons that exhibit proper neurite outgrowth and axonal and dendritic morphology. While many protein coding genes are shown to be involved in neuronal maturation, the role of microRNAs (miRNAs in this process is also becoming evident. We here report that blocking miRNA biogenesis in differentiated neurons results in microcephaly-like phenotypes in the postnatal mouse brain. The smaller brain defect is not caused by defective neurogenesis, altered neuronal migration or significant neuronal cell death. Surprisingly, a dramatic increase in neuronal packing density within the postnatal brain is observed. Loss of miRNA function causes shorter neurite outgrowth and smaller soma size of mature neurons in vitro. Our results reveal the impact of miRNAs on normal development of neuronal morphology and brain function. Because neurite outgrowth is critical for neuroregeneration, our studies further highlight the importance of miRNAs in the treatment of neurodegenerative diseases.

  19. Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans.

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    Eva María Medina-Rodríguez

    Full Text Available During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs, a cell type that is a significant proportion of the total cells (3-8% in the adult central nervous system (CNS of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair.

  20. 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.

  1. Strong inhibition of replicative DNA synthesis in the developing rat cerebral cortex and glioma cells by roscovitine.

    Science.gov (United States)

    Yakisich, Juan Sebastian; Vita, Marina Fernanda; Siden, Ake; Tasat, Deborah Ruth; Cruz, Mabel

    2010-06-01

    The effects of the cyclin-dependent kinase inhibitors roscovitine and olomoucine on DNA synthesis rate during normal rat brain development were studied by using short time (90 min) incubation. Both purine analogues at 100 microM concentration decreased the DNA synthesis of rat cerebral cortex in an age-dependent manner. The maximum inhibitory effect (approximately 90% for roscovitine, approximately 60% for olomoucine) occurred in rats of 2-13 days postnatal age. In adult rats (> 60 days postnatal age), the effect of both purine analogues was low. Roscovitine even at 200 microM concentration did not inhibit the fraction of DNA synthesis insensitive to hydroxyurea (unscheduled DNA synthesis (UDS)). In addition, in the RG2 rat glioma model, roscovitine produced a strong inhibition of DNA synthesis in glioma cells when compared to adult normal tissue. Since in adult rat brain more than 60% of DNA synthesis is related to DNA repair, usually measured as UDS, our results indicate that roscovitine strongly blocks ongoing DNA synthesis connected with replicative processes.

  2. Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease.

    Science.gov (United States)

    Ravid, Rivka; Ferrer, Isidro

    2012-04-01

    Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach.

  3. 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.

  4. Modulation of antioxidant enzyme expression by PTU-induced hypothyroidism in cerebral cortex of postnatal rat brain.

    Science.gov (United States)

    Bhanja, Shravani; Jena, Srikanta

    2013-01-01

    This study aimed to elucidate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters and expression of antioxidant enzymes in cerebral cortex of rat brain during postnatal development. A significant decrease in levels of lipid peroxidation and H(2)O(2) were seen in 7 and 30 days old PTU-treated rats with respect to their controls. Significantly decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old PTU-treated rats as compared to their respective controls. However, increase in translated product of CAT was seen in all age groups of PTU-treated rats. Glutathione peroxidase activity was decreased in 7 days and increased in 15 days old PTU-treated rats with respect to their control groups. Histological sections clearly show a decline in neuronal migration with neurons packed together in the hypothyroid group as compared to the control.

  5. 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.

  6. A nuclear localized protein ZCCHC9 is expressed in cerebral cortex and suppresses the MAPK signal pathway

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The CCHC-type zinc finger motif has numerous biological activities (such as DNA binding and RNA binding) and can also mediate protein-protein interaction. This article gives a primary report about the human ZCCHC9 gene. Protein ZCCHC9 contains four CCHC motifs and is highly conserved in humans, mice, and rats. The whole cDNA sequence of the ZCCHC9 gene has been amplified by PCR and a number of plasmids have been constructed for further study. The results show that ZCCHC9 is localized in the nucleus, and especially concentrated in the nucleolus. It is highly expressed in the brain and testicles of the mouse. This has been confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). In situ hybridization of the mouse brain indicates that ZCCHC9 is mainly expressed in the cerebral cortex. Reporter gene assay shows that ZCCHC9 suppresses the transcription activities of NF-kappa B and SRE,and may play roles in the Mitogen-Activated Protein Kinase (MAPK) signaling transduction pathway.

  7. Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats.

    Science.gov (United States)

    Pederzolli, Carolina Didonet; Rockenbach, Francieli Juliana; Zanin, Fernanda Rech; Henn, Nicoli Taiana; Romagna, Eline Coan; Sgaravatti, Angela M; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir; de Mattos Dutra, Angela; Dutra-Filho, Carlos S

    2009-06-01

    N-acetylaspartic acid (NAA) is the biochemical hallmark of Canavan Disease, an inherited metabolic disease caused by deficiency of aspartoacylase activity. NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD. This neurodegenerative disorder is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30-day-old rats. NAA significantly reduced total radical-trapping antioxidant potential, catalase and glucose 6-phosphate dehydrogenase activities, whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced. Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA. In contrast, NAAG did not alter any of the oxidative stress parameters tested. Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins, which could be involved in the neurotoxicity of NAA accumulation in CD patients.

  8. Cognitive impairment and transmitter-specific pre- and postsynaptic changes in the rat cerebral cortex during ageing.

    Science.gov (United States)

    Majdi, Maryam; Ribeiro-da-Silva, Alfredo; Cuello, A Claudio

    2007-12-01

    Recent studies suggest that age-related cognitive decline is correlated with an excitatory-inhibitory imbalance in synaptic discharges on pyramidal neurons. This study focuses on whether ageing and cognitive status correlates with relative numbers of excitatory and inhibitory presynaptic boutons. We investigated the density of excitatory and inhibitory presynaptic inputs across several areas of the rat cerebral cortex in young and aged male Fischer 344 rats. Aged animals were segregated into aged cognitively impaired (AI) and aged cognitively unimpaired (AU) groups using the Morris water maze. We applied immunohistochemistry to reveal the majority of excitatory and inhibitory presynaptic boutons captured with confocal microscopy and quantitative image analysis. A gradual decline in the density of excitatory and inhibitory presynaptic boutons occurred from young to AU to AI animals; however, the ratios of excitatory to inhibitory presynaptic bouton densities were not significantly altered. We further investigated the density of receptor scaffolding proteins representing key excitatory and inhibitory receptor postsynaptic sites, using antibodies against specific markers of excitatory and inhibitory postsynaptic densities, respectively. Significant changes in the ratios of excitatory to inhibitory postsynaptic densities were observed only in AI compared to young rats.

  9. Polychlorinated biphenyls, organochlorinated pesticides, and polybrominated diphenyl ethers in the cerebral cortex of wild river otters (Lontra canadensis)

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Niladri [National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, Ottawa, Ontario, K1A 0H3 (Canada)]. E-mail: nbasu@uottawa.ca; Scheuhammer, Anton M. [National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, Ottawa, Ontario, K1A 0H3 (Canada); O' Brien, Mike [Furbearers and Upland Game, Nova Scotia Department of Natural Resources, Kentville, Nova Scotia, B4N 4E5 (Canada)

    2007-09-15

    We measured the levels of ortho-substituted polychlorinated biphenyls (PCB), organochlorinated pesticides (OCP), and polybrominated diphenyl ethers (PBDE) in the cerebral cortex of river otters (Lontra canadensis) trapped from Ontario and Nova Scotia between 2002 and 2004. The mean concentration of total PCBs was 70.9 {+-} 12.1 ng/g l.w., and congeners 153, 180 and 138 accounted for nearly 60% of the sum. The mean concentration of total OCPs was 21.2 {+-} 3.7 ng/g l.w., and hexachlorobenzene (32.6% of total) and DDE (28.1%) accounted for the majority. The mean concentration of total PBDEs was 3.2 {+-} 0.6 ng/g l.w., and congeners 99 (44.9%), 153 (30.5%), and 100 (24.7%) were measured at the indicated percentages. There was no relationship between these residue data and concentrations of brain mercury or neurochemical receptors and enzymes as determined in earlier studies on these same animals. - River otters accumulated PCBs, OCPs, and PBDEs, but at levels below thresholds for neurotoxic effects.

  10. Germinal zones in the developing cerebral cortex of ferret: ontogeny, cell cycle kinetics, and diversity of progenitors.

    Science.gov (United States)

    Reillo, Isabel; Borrell, Víctor

    2012-09-01

    Expansion and folding of the cerebral cortex are landmark features of mammalian brain evolution. This is recapitulated during embryonic development, and specialized progenitor cell populations known as intermediate radial glia cells (IRGCs) are believed to play central roles. Because developmental mechanisms involved in cortical expansion and folding are likely conserved across phylogeny, it is crucial to identify features specific for gyrencephaly from those unique to primate brain development. Here, we studied multiple features of cortical development in ferret, a gyrencephalic carnivore, in comparison with primates. Analyzing the combinatorial expression of transcription factors, cytoskeletal proteins, and cell cycle parameters, we identified a combination of traits that distinguish in ferret similar germinal layers as in primates. Transcription factor analysis indicated that inner subventricular zone (ISVZ) and outer subventricular zone (OSVZ) may contain an identical mixture of progenitor cell subpopulations in ferret. However, we found that these layers emerge at different time points, differ in IRGC abundance, and progenitors have different cell cycle kinetics and self-renewal dynamics. Thus, ISVZ and OSVZ are likely distinguished by genetic differences regulating progenitor cell behavior and dynamics. Our findings demonstrate that some, but not all, features of primate cortical development are shared by the ferret, suggesting a conserved role in the evolutionary emergence of gyrencephaly.

  11. What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus.

    Science.gov (United States)

    Fjell, Anders M; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B

    2014-06-01

    What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology.

  12. 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.

  13. Ultrastructure of focal cerebral cortex tissue from rats with focal cortical dysplasia

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Developing a model of focal cortical dysplasia in microgyrus and observing the ultrastructure of focal tissue is of important significance for analyzing the pathology of cortical developmental disorder and the factors of structural changes. OBJECTIVE:This study was to observe the pathological characteristics of focal tissue around the microgyrus of rats with cortical developmental disorder using an electron microscope,so as to analyze the causes associated with cerebral cortical developmental disorder. DESIGN:A randomized controlled animal experiment. SETTING:The First Affiliated Hospital of Chongqing Medical University. MATERIALS:This study was carried out in the Chongqing Key Laboratory of Neurology,Room for Electron Microscope of Chongqing Medical University,and Laboratory Animal Center,Research Institute of Surgery,Daping Hospital,Third Military Medical University of Chinese PLA between January 2004 and August 2006.Eighteen healthy newborn male Wistar rats,weighing 3.0 - 6.0 g,provided by the Laboratory Animal Center,Daping Hospital,Third Military Medical University of Chinese PLA,were involved in this study.The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals.Probes (Chongqing Wire & Cable Factory,China) were made of copper core wire with diameter of 1 mm.METHODS:The rats were randomly divided into 3 groups with 6 in each:normal control group,liquid nitrogen injured group and sham-operation group.①In the liquid nitrogen injured group,a blunt probe frozen by liquid nitrogen was placed on fronto-parietal crinial bone of rats for 8 s.A 3 - 5 cm of microgyrus was induced in the unilateral cerebral sensory cortical area.In the sham-operation group,probe was placed at the room temperature.In the normal control group,rats were untouched.② The conscious state and electrical activity of brain of rats in each group were observed.③ 2-3 mm thickness of hippocampal tissue with coronary section was taken

  14. Expression of c-Fos protein and nitricoxide synthase in neurons of cerebral cortex from fetal rats in hypoxia and protective role of Angelica sinensis

    Institute of Scientific and Technical Information of China (English)

    Hong Yu; Hongxian Zhao; Yuling Wu

    2006-01-01

    BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus.OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia.DESIGN: Randomized control experiment.SETTING: Department of Histology and Embryology, Luzhou Medical College.MATERIALS: Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310).METHODS: This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ① Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8:00 am next day.On the 15th conceiving day,all conceiving rats were divided randomly into three groups:control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia.Hypoxia group:Rats were injected with the same volume of saline.Control group:Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in

  15. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

    2014-01-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  16. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells.

    Science.gov (United States)

    Tan, Jielu; Zheng, Xiangrong; Zhang, Shanshan; Yang, Yujia; Wang, Xia; Yu, Xiaohe; Zhong, Le

    2014-10-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into five groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular endothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. The cerebral palsy model was established by ligating the left common carotid artery followed by exposure to hypoxia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. After transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vascular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for finding water and the finding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. These findings indicate that the transplantation of vascular endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deficits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  17. Combined transcriptome analysis of fetal human and mouse cerebral cortex exposed to alcohol.

    Science.gov (United States)

    Hashimoto-Torii, Kazue; Kawasawa, Yuka Imamura; Kuhn, Alexandre; Rakic, Pasko

    2011-03-08

    Fetal exposure to environmental insults increases the susceptibility to late-onset neuropsychiatric disorders. Alcohol is listed as one of such prenatal environmental risk factors and known to exert devastating teratogenetic effects on the developing brain, leading to complex neurological and psychiatric symptoms observed in fetal alcohol spectrum disorder (FASD). Here, we performed a coordinated transcriptome analysis of human and mouse fetal cerebral cortices exposed to ethanol in vitro and in vivo, respectively. Up- and down-regulated genes conserved in the human and mouse models and the biological annotation of their expression profiles included many genes/terms related to neural development, such as cell proliferation, neuronal migration and differentiation, providing a reliable connection between the two species. Our data indicate that use of the combined rodent and human model systems provides an effective strategy to reveal and analyze gene expression changes inflicted by various physical and chemical environmental exposures during prenatal development. It also can potentially provide insight into the pathogenesis of environmentally caused brain disorders in humans.

  18. 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.

  19. Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity.

    Science.gov (United States)

    Berbel, P; Navarro, D; Ausó, E; Varea, E; Rodríguez, A E; Ballesta, J J; Salinas, M; Flores, E; Faura, C C; de Escobar, G Morreale

    2010-06-01

    Hypothyroxinemia affects 35-50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers' organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.

  20. Trends and properties of human cerebral cortex: correlations with cortical myelin content.

    Science.gov (United States)

    Glasser, Matthew F; Goyal, Manu S; Preuss, Todd M; Raichle, Marcus E; Van Essen, David C

    2014-06-01

    "In vivo Brodmann mapping" or non-invasive cortical parcellation using MRI, especially by measuring cortical myelination, has recently become a popular research topic, though myeloarchitectonic cortical parcellation in humans previously languished in favor of cytoarchitecture. We review recent in vivo myelin mapping studies and discuss some of the different methods for estimating myelin content. We discuss some ways in which myelin maps may improve surface registration and be useful for cross-modal and cross-species comparisons, including some preliminary cross-species results. Next, we consider neurobiological aspects of why some parts of cortex are more myelinated than others. Myelin content is inversely correlated with intracortical circuit complexity - in general, more myelin content means simpler and perhaps less dynamic intracortical circuits. Using existing PET data and functional network parcellations, we examine metabolic differences in the differently myelinated cortical functional networks. Lightly myelinated cognitive association networks tend to have higher aerobic glycolysis than heavily myelinated early sensory-motor ones, perhaps reflecting greater ongoing dynamic anabolic cortical processes. This finding is consistent with the hypothesis that intracortical myelination may stabilize intracortical circuits and inhibit synaptic plasticity. Finally, we discuss the future of the in vivo myeloarchitectural field and cortical parcellation--"in vivo Brodmann mapping"--in general.

  1. Task-driven intra- and interarea communications in primate cerebral cortex

    Science.gov (United States)

    Tauste Campo, Adrià; Martinez-Garcia, Marina; Nácher, Verónica; Luna, Rogelio; Romo, Ranulfo; Deco, Gustavo

    2015-01-01

    Neural correlations during a cognitive task are central to study brain information processing and computation. However, they have been poorly analyzed due to the difficulty of recording simultaneous single neurons during task performance. In the present work, we quantified neural directional correlations using spike trains that were simultaneously recorded in sensory, premotor, and motor cortical areas of two monkeys during a somatosensory discrimination task. Upon modeling spike trains as binary time series, we used a nonparametric Bayesian method to estimate pairwise directional correlations between many pairs of neurons throughout different stages of the task, namely, perception, working memory, decision making, and motor report. We find that solving the task involves feedforward and feedback correlation paths linking sensory and motor areas during certain task intervals. Specifically, information is communicated by task-driven neural correlations that are significantly delayed across secondary somatosensory cortex, premotor, and motor areas when decision making takes place. Crucially, when sensory comparison is no longer requested for task performance, a major proportion of directional correlations consistently vanish across all cortical areas. PMID:25825731

  2. Affinity labeling of muscarinic receptors in rat cerebral cortex with a photolabile antagonist.

    Science.gov (United States)

    Amitai, G; Avissar, S; Balderman, D; Sokolovsky, M

    1982-01-01

    Highly potent photoaffinity probes for muscarinic binding sites were prepared by the incorporation of an azido group into the benzilic acid moiety in two compound, 3-quinuclidinyl benzilate (3QNB) and N-methyl-4-piperidyl benzilate (4NMPB). Inactivation of muscarinic sites in rat cortex depends on the formation of a reversible complex with the azides prior to their photolytic conversion to the highly reactive nitrenes. During photolysis, radiolabeled azido-4NMPB interacted specifically and with high affinity (Kd = 1.06 nM) with the muscarinic receptors, and the ligand could be covalently incorporated into a macromolecule of about 86,000 Mr, presumably the muscarinic receptor. The incorporation was almost stoichiometric when compared to determination of receptor density by reversible ligands. Atropine (10 microM) afforded specific protection (greater than 83%) of the receptor against inactivation by azido-[3H]4NMPB. This compound and the other ligands described here (i.e., amino-4NMPB, amino-3QNB, and azido-3QNB) represent powerful potential probes for the biochemical isolation and characterization of muscarinic receptors. Images PMID:6952181

  3. 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

  4. Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.

    Science.gov (United States)

    Xiong, Zhi-Qi; Qian, Weihua; Suzuki, Katsuaki; McNamara, James O

    2003-02-01

    The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.

  5. Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex

    Science.gov (United States)

    McCreery, Douglas; Cogan, Stuart; Kane, Sheryl; Pikov, Victor

    2016-06-01

    Objective. To quantify relations between the neuronal activity recorded with chronically-implanted intracortical microelectrodes and the histology of the surrounding tissue, using radial distance from the tip sites and time after array implantation as parameters. Approach. ‘Utah’-type intracortical microelectrode arrays were implanted into cats’ sensorimotor cortex for 275-364 days. The brain tissue around the implants was immuno-stained for the neuronal marker NeuN and for the astrocyte marker GFAP. Pearson’s product-moment correlations were used to quantify the relations between these markers and the amplitudes of the recorded neuronal action potentials (APs) and their signal-to-noise ratios (S/N). Main results. S/N was more stable over post-implant time than was AP amplitude, but its increased correlation with neuronal density after many months indicates ongoing loss of neurons around the microelectrodes. S/N was correlated with neuron density out to at least 140 μm from the microelectrodes, while AP amplitude was correlated with neuron density and GFAP density within ˜80 μm. Correlations between AP amplitude and histology markers (GFAP and NeuN density) were strongest immediately after implantation, while correlation between the neuron density and S/N was strongest near the time the animals were sacrificed. Unlike AP amplitude, there was no significant correlation between S/N and density of GFAP around the tip sites. Significance. Our findings indicate an evolving interaction between changes in the tissue surrounding the microelectrodes and the microelectrode’s electrical properties. Ongoing loss of neurons around recording microelectrodes, and the interactions between their delayed electrical deterioration and early tissue scarring around the tips appear to pose the greatest threats to the microelectrodes’ long-term functionality.

  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.

  7. The Effect of the Oral Administration of Salvia Rhytidia Extract on Neural Cell Numbers of Cerebral Cortex and Hippocampus Following Ischemia-Reperfusion in Rat

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    R Haghjoo

    2015-05-01

    Full Text Available Backgrounds & aim: Forebrain ischemia induces complete interruption of brain blood flow and neuronal injury. In the present study the effect of Salvia rhytidia extract on cell numbers of the cerebral cortex and different hippocampal regions following ischemia-reperfusion (IR was evaluated. Methods: In the present experimental study, Thirty-five adult male rats were divided into 7 groups of 5 rats. Control group (1, sham group (3, and 2, 4, 5, 6, and 7 as ischemic groups. (2, 4, 5, 6, 7. Left common carotid and left vertebral arteries were occluded by tourniquet for 10 min. Group 2 received no drug .sham group (3 received normal saline without ischemia. Group 4 received Salvia (3.2mg/kg and group 5 received silymarin (50 mg/kg, 2 h after ischemia. Group 6 received the same dose of Salvia and group 7 received the same dose of silymarin 0, 24, 48, and 72 hrs before ischemia. After 24 h reperfusion, the brains of rats were prepared for histological studies. The cells were counted and cerebral and hippocampal tissue sections stained by hematoxylin and eosin. The data were analyzed by One-way ANOVA and Duncan as posthoc test. Results: Significant decrease was observed in the neural cell numbers of cerebral cortex and pyramidal layer of CA1 and CA2 regions of the hippocampus in groups 2, 4 and 5 compared to control group (p=00000. No significant decrease was observed in neural cell numbers of cerebral cortex and all hippocampal regions in groups 3, 6, 7. Pyramidal layer of CA3 and granular layer of dentate gyrus regions of the hippocampus in groups 2, 4 and 5 compared to control. Conclusion: Saliva extract with aintoxidan effect similar to silymarin protects the forebrain from ischemia injuries and reperfusion.

  8. Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

    Science.gov (United States)

    Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

    2016-10-01

    Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  9. Increased gamma-aminobutyric acid receptor function in the cerebral cortex of myoclonic calves with an hereditary deficit in glycine/strychnine receptors.

    Science.gov (United States)

    Lummis, S C; Gundlach, A L; Johnston, G A; Harper, P A; Dodd, P R

    1990-08-01

    Inherited congenital myoclonus (ICM) of Poll Hereford cattle is a neurological disease in which there are severe alterations in spinal cord glycine-mediated neurotransmission. There is a specific and marked decrease, or defect, in glycine receptors and a significant increase in neuronal (synaptosomal) glycine uptake. Here we have examined the characteristics of the cerebral gamma-aminobutyric acid (GABA) receptor complex, and demonstrate that the malfunction of the spinal cord inhibitory system is accompanied by a change in the major inhibitory system in the cerebral cortex. In synaptic membrane preparations from ICM calves, both high-and low-affinity binding sites for the GABA agonist [3H]muscimol were found (KD = 9.3 +/- 1.5 and 227 +/- 41 nM, respectively), whereas only the high-affinity site was detectable in controls (KD = 14.0 +/- 3.1 nM). The density and affinity of benzodiazepine agonist binding sites labelled by [3H]diazepam were unchanged, but there was an increase in GABA-stimulated benzodiazepine binding. The affinity for t-[3H]butylbicyclo-o-benzoate, a ligand that binds to the GABA-activated chloride channel, was significantly increased in ICM brain membranes (KD = 148 +/- 14 nM) compared with controls (KD = 245 +/- 33 nM). Muscimol-stimulated 36Cl- uptake was 12% greater in microsacs prepared from ICM calf cerebral cortex, and the uptake was more sensitive to block by the GABA antagonist picrotoxin. The results show that the characteristics of the GABA receptor complex in ICM calf cortex differ from those in cortex from unaffected calves, a difference that is particularly apparent for the low-affinity, physiologically relevant GABA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.

    Science.gov (United States)

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2013-03-01

    The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. Associative tuning plasticity in the primary auditory cortex (A1) constitutes a well-characterized candidate specific memory substrate that is ubiquitous across species, tasks and motivational states. When tone predicts reinforcement, the tuning of cells in A1 shifts toward or to the signal frequency within its tonotopic map, producing an over-representation of behaviorally important sounds. Tuning shifts have the cardinal attributes of forms of memory, including associativity, specificity, rapid induction, consolidation and long-term retention and are therefore likely memory representations. We hypothesized that the BLA strengthens memories by increasing their cortical representations. We recorded multiple unit activity from A1 of rats that received a single discrimination training session in which two tones (2.0 s) separated by 1.25 octaves were either paired with brief electrical stimulation (400 ms) of the BLA (CS+) or not (CS-). Frequency response areas generated by presenting a matrix of test tones (0.5-53.82 kHz, 0-70 dB) were obtained before training and daily for 3 weeks post-training. Tuning both at threshold and above threshold shifted predominantly toward the CS+ beginning on day 1. Tuning shifts were maintained for the entire 3 weeks. Absolute threshold and bandwidth decreased, producing less enduring increases in sensitivity and selectivity. BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the

  11. Structural changes in pyramidal cell dendrites and synapses in the unaffected side of the sensorimotor cortex following transcranial magnetic stimulation and rehabilitation training in a rat model of focal cerebral infarct

    Institute of Scientific and Technical Information of China (English)

    Chuanyu Liu; Surong Zhou; Xuwen Sun; Zhuli Liu; Hongliang Wu; Yuanwu Mei

    2011-01-01

    Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex.These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.

  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. 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.

  14. 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.

  15. 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

    2013-01-01

    [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. PMID:24396190

  16. Visinin-like neuronal calcium sensor proteins regulate the slow calcium-activated afterhyperpolarizing current in the rat cerebral cortex

    Science.gov (United States)

    Villalobos, Claudio; Andrade, Rodrigo

    2010-01-01

    Many neurons in the nervous systems express afterhyperpolarizations that are mediated by a slow calcium-activated potassium current. This current shapes neuronal firing and is inhibited by neuromodulators, suggesting an important role in the regulation of neuronal function. Surprisingly, very little is currently known about the molecular basis for this current or how it is gated by calcium. Recently, the neuronal calcium sensor protein hippocalcin was identified as a calcium sensor for the slow afterhyperpolarizing current in the hippocampus. However, while hippocalcin is very strongly expressed in the hippocampus, this protein shows a relatively restricted distribution in the brain. Furthermore, the genetic deletion of this protein only partly reduces the slow hyperpolarizing current in hippocampus. These considerations question whether hippocalcin can be the sole calcium sensor for the slow afterhyperpolarizing current. Here we use loss of function and overexpression strategies to show that hippocalcin functions as a calcium sensor for the slow afterhyperpolarizing current in the cerebral cortex, an area where hippocalcin is expressed at much lower levels than in hippocampus. In addition we show that neurocalcin δ, but not VILIP-2, can also act as a calcium sensor for the slow afterhyperpolarizing current. Finally we show that hippocalcin and neurocalcin δ both increase the calcium sensitivity of the afterhyperpolarizing current but do not alter its sensitivity to inhibition by carbachol acting through the Gαq-11-PLCβ signaling cascade. These results point to a general role for a subgroup of visinin-like neuronal calcium sensor proteins in the activation of the slow calcium-activated afterhyperpolarizing current. PMID:20980592

  17. Depolarizing and calcium-mobilizing stimuli fail to enhance synthesis and release of endocannabinoids from rat brain cerebral cortex slices.

    Science.gov (United States)

    Sarmad, Sarir; Alexander, Stephen P H; Barrett, David A; Marsden, Charles A; Kendall, David A

    2011-05-01

    The concentrations of the endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonylethanolamine (anandamide) were examined in rat brain cerebral cortex slices and surrounding medium. Basal concentrations of endocannabinoids were similar to those identified previously in rat brain, with anandamide content being much lower (19 pmol/g) than that of 2-AG (7300 pmol/g). In contrast, basal concentrations in the surrounding medium were proportionally much lower for 2-arachidonoylglycerol (16 pmol/mL) compared to anandamide (0.6 pmol/mL). Incubation of slices with glutamate receptor agonists, depolarizing concentrations of KCl, or ionomycin failed to alter tissue concentrations of endocannabinoids, while endocannabinoids in the medium were unaltered by elevated KCl. Cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester, an inhibitor of fatty acid amide hydrolase, significantly enhanced tissue concentrations of anandamide (and related N-acylethanolamines), without altering 2-AG, while evoking proportional elevations of anandamide in the medium. Removal of extracellular calcium ions failed to alter tissue concentrations of anandamide, but significantly reduced 2-AG in the tissue by 90% and levels in the medium to below the detection limit. Supplementation of the medium with 50 μM N-oleoylethanolamine only raised tissue concentrations of N-oleoylethanolamine in the presence of cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester and failed to alter either tissue or medium anandamide or 2-AG concentrations. These results highlight the ongoing turnover of endocannabinoids, and the importance of calcium ions in maintaining 2-AG concentrations in this tissue.

  18. 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.

  19. 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.

  20. The myeloarchitectonic studies on the human cerebral cortex of the Vogt-Vogt school, and their significance for the interpretation of functional neuroimaging data.

    Science.gov (United States)

    Nieuwenhuys, Rudolf

    2013-03-01

    The human cerebral cortex contains numerous myelinated fibres, many of which are concentrated in tangentially organized layers and radially oriented bundles. The spatial organization of these fibres is by no means homogeneous throughout the cortex. Local differences in the thickness and compactness of the fibre layers, and in the length and strength of the radial bundles renders it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification and delineation of such areas is known as myeloarchitectonics. There is another, closely related neuroanatomical subdiscipline, named cytoarchitectonics. The aims and scope of this subdiscipline are the same as those of myeloarchitectonics, viz. parcellation. However, this subdiscipline focuses, as its name implies, on the size, shape and arrangement of the neuronal cell bodies in the cortex, rather than on the myelinated fibres. At the beginning of the twentieth century, two young investigators, Oskar and Cécile Vogt founded a centre for brain research, aimed to be devoted to the study of the (cyto + myelo) architecture of the cerebral cortex. The study of the cytoarchitecture was entrusted to their collaborator Korbinian Brodmann, who gained great fame with the creation of a cytoarchitectonic map of the human cerebral cortex. Here, we focus on the myeloarchitectonic studies on the cerebral cortex of the Vogt-Vogt school, because these studies are nearly forgotten in the present attempts to localize functional activations and to interprete findings in modern neuroimaging studies. Following introductory sections on the principles of myeloarchitectonics, and on the achievements of three myeloarchitectonic pioneers who did not belong to the Vogt-Vogt school, the pertinent literature is reviewed in some detail. These studies allow the conclusion that the human neocortex contains about 185 myeloarchitectonic areas, 70 frontal, 6 insular, 30 parietal, 19 occipital

  1. Creatine administration prevents Na+,K+-ATPase inhibition induced by intracerebroventricular administration of isovaleric acid in cerebral cortex of young rats.

    Science.gov (United States)

    Ribeiro, César Augusto João; Leipnitz, Guilhian; Amaral, Alexandre Umpierrez; de Bortoli, Giorgia; Seminotti, Bianca; Wajner, Moacir

    2009-03-25

    Isovaleric acidemia (IVAcidemia) is an inborn error of metabolism due to deficiency of isovaleryl-CoA dehydrogenase activity, leading to predominant accumulation of isovaleric acid (IVA). Patients affected by IVAcidemia suffer from acute episodes of encephalopathy, whose underlying mechanisms are poorly known. In the present study we investigated whether an intracerebroventricular injection of IVA could compromise energy metabolism in cerebral cortex of young rats. IVA administration significantly inhibited (14)CO(2) production from acetate (22%) and citrate synthase activity (20%) in cerebral cortex homogenates prepared 24 h after injection. However, no alterations of these parameters were observed 2 h after injection. In contrast, no significant differences were found in the activities of succinate dehydrogenase, isocitrate dehydrogenase, electron transfer chain complexes or creatine kinase in rats sacrificed 2 or 24 h after IVA administration. Moreover, IVA injection significantly inhibited Na(+),K(+)-ATPase activity (25%) in cerebral cortex of rats 2 or 24 h after IVA administration, while pre-treatment of rats with creatine completely prevented the inhibitory effects of IVA on Na(+),K(+)-ATPase. In conclusion, in vivo administration of IVA inhibits the citric acid cycle probably through the enzyme citrate synthase, as well as Na(+),K(+)-ATPase, a crucial enzyme responsible for maintaining the basal potential membrane necessary for a normal neurotransmission. It is presumed that inhibition of these activities may be involved in the pathophysiology of the neurological dysfunction of isovaleric academic patients. The present findings are of particular interest because treatment with creatine supplementation may represent a potential novel adjuvant therapeutic strategy in IVAcidemia.

  2. 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.

  3. Microstructural parcellation of the human cerebral cortex – from Brodmann's post-mortem map to in vivo mapping with high-field magnetic resonance imaging

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    Stefan Geyer

    2011-02-01

    Full Text Available The year 2009 marked the 100th anniversary of the publication of the famous brain map of Korbinian Brodmann. Although a "classic" guide to microanatomical parcellation of the cerebral cortex, it is – from today's state-of-the-art neuroimaging perspective – problematic to use Brodmann's map as a structural guide to functional units in the cortex. In this article we discuss some of the reasons, especially the problematic compatibility of the "post-mortem world" of microstructural brain maps with the "in vivo world" of neuroimaging. We conclude with some prospects for the future of in vivo structural brain mapping: a new approach which has the enormous potential to make direct correlations between microstructure and function in living human brains: "in vivo Brodmann mapping" with high-field magnetic resonance imaging.

  4. Changes in synapse quantity and growth associated protein 43 expression in the motor cortex of focal cerebral ischemic rats following catalpol treatment

    Institute of Scientific and Technical Information of China (English)

    Dong Wan; Huifeng Zhu; Yong Luo; Peng Xie

    2011-01-01

    The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using electrocoagulation. The rats were intraperitoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week. Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.

  5. The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation.

    Science.gov (United States)

    Chan, S-Y; Martín-Santos, A; Loubière, L S; González, A M; Stieger, B; Logan, A; McCabe, C J; Franklyn, J A; Kilby, M D

    2011-06-01

    Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7–20 weeks gestation) and during retinoic acid induced neurodifferentiation of the human N-Tera-2 (NT2) cell line, in triiodothyronine (T3) replete and T3-depleted media. Compared with adult cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. From the early first trimester, immunohistochemistry localised MCT8 and MCT10 to the microvasculature and to undifferentiated CNS cells. With neurodifferentiation, NT2 cells demonstrated declining T3 uptake, accompanied by reduced expressions of MCT8, LAT1, CD98 and OATP4A1. T3 depletion significantly reduced MCT10 and LAT2 mRNA expression at specific time points during neurodifferentiation but there were no effects upon T3 uptake, neurodifferentiation marker expression or neurite lengths and branching. MCT8 repression also did not affect NT2 neurodifferentiation. In conclusion, many TH transporters are expressed in the human fetal cerebral cortex from the first trimester, which could regulate cellular TH supply during early development. However, human NT2 neurodifferentiation is not dependent upon T3 or MCT8 and there were no compensatory changes to promote T3 uptake in a T3-depleted environment.

  6. G protein-linked receptors labeled by [3H]histamine in guinea pig cerebral cortex. I. Pharmacological characterization [corrected].

    Science.gov (United States)

    Sinkins, W G; Kandel, M; Kandel, S I; Schunack, W; Wells, J W

    1993-04-01

    Binding of histamine to washed membranes from guinea pig cerebral cortex can be described empirically as two classes of distinct and independent sites (log IP1 = -8.45 +/- 0.02, R1;t = 98 +/- 6 pmol/g of protein; log KP2 = -6.34 +/- 0.22, R2.t = 990 +/- 60 pmol/g of protein). At 1.4 nm [3H]histamine, the kinetics of association and dissociation are biexponential. The values of k-Pj/k+Pj calculated for parallel one-step processes agree well with the corresponding values of KPj. Both k-p1 and k-P2 are increased by 0.1 mM guanylylimidodiphosphate; apparent capacity at equilibrium is reduced for both classes of sites, with little or no change in KP1 or KP2. Twenty-six H2 and H3 agonists and antagonists block access of [3H]histamine to the same sites, and the binding patterns reveal either one or two hyperbolic terms [i.e., sigma nj = 1 F' jKj/(Kj+[L])]. Two terms are required for six agonists and six antagonists, and F'2 varies widely from ligand to ligand. Also, the quantity log (K2/K1) is correlated with F'1 among agonists but with F'2 among antagonists (K1 < K2). The pharmacological selectivity is suggestive of both H2 and H3 receptors. An H2 specificity emerges from the appropriate values of Kj for 12 H2 agonists (i.e., K1 when n = 1 and K2 when n = 2; p = 0.00045), although a specificity distinct from that of H2 receptors is found with H2 antagonists. An H3 specificity emerges from the inhibitory potencies (IC50) of eight H3 agonists (p = 0.00025) and eight H3 antagonists (p = 0.0019); also, the sites labeled by [3H]histamine resemble H3 receptors reportedly labeled by N alpha-[3H]methylhistamine and (R)-alpha-[3H]methylhistamine. Ligand-dependent differences in F'2 are inconsistent with the notion of distinct and independent sites, and the tendency of antagonists to promote the sites of weaker affinity (F'2) argues against a ligand-regulated equilibrium between two states. The physical significance of the binding parameters is therefore unclear. The failure to

  7. Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

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    Holman David W

    2007-07-01

    Full Text Available Abstract Background The arachnoid granulations (AGs are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex. Methods En face images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area. Results The total brain average surface area of AGs was 78.53 ± 13.13 mm2 (n = 35 and average AG proportional involvement was 57.71 × 10-4 ± 7.65 × 10-4. Regression analysis confirmed the reproducibility of AG identification between independent researchers with r2 = 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae. Conclusion The data obtained on the spatial distribution and en face surface area of AGs will be used in an in vitro model of CSF outflow. With an increase in the number of samples, this analysis technique can be used

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

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    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.

  9. PiB fails to map amyloid deposits in cerebral cortex of aged dogs with canine cognitive dysfunction

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    Rikke eFast

    2013-12-01

    Full Text Available 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 ([11C]PiB. Structural MRI 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 [11C]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 [11C]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 [11C]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 [11C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.

  10. Alteration in IGF-I binding in the cerebral cortex and cerebellum of neonatal rats during protein-calorie malnutrition.

    Science.gov (United States)

    Maheshwari, H G; Mermelstein, S; vonSchlegell, A S; Shambaugh, G E

    1997-03-01

    Neonatal brain development in the rat is adversely affected by malnutrition. Alterations in tissue binding of IGF-I in the malnourished brain were tested in rat pups from mothers who were fed a 20% protein diet (C) or a 4% protein diet (M) starting from day 21 of gestation and continued throughout suckling. IGF-I binding in both cortex and cerebellum decreased progressively in C and M groups from day 6 to day 13. At day 9, 11, and 13, the binding was significantly greater (p < 0.02) in M compared to C groups. To investigate whether these changes might be related to the alteration in receptor activity, membranes were incubated with 125I-IGF in the presence of excess insulin with or without unlabeled IGF-I. In the absence of insulin, specific IGF-I binding in the M group was increased by 41.8 +/- 13.8% (mean +/- SEM p < 0.05) relative to C group. Insulin produced a consistent but incomplete inhibition of binding in both C and M, of 75% and 67% respectively. In addition, the specific IGF-I binding in the presence of insulin was increased in M group by 70.2 +/- 9.4% relative to C, p < 0.05. To characterize the nature of this binding, cerebral cortical membranes, from both groups, incubated with 125I-IGF-I were cross-linked, and electrophoresed on 6% and 10% SDS-PAGE gels under reducing conditions. Autoradiography of the 6% gel showed two specific bands at 115 kD and 240 kD, consistent with monomeric and dimeric forms of the IGF-I receptor, which were inhibited by excess insulin. In contrast, a 10% gel showed an additional band at 35 kD (IGF-binding protein) that was not inhibited by insulin. In both gels, membrane preparations from the M group showed a heightened intensity of the bands relative to C. The increase in binding protein relative to the receptor suggests a disequilibrium that may limit the availability of exogenous IGF-I to the tissues.

  11. Neural stem cells and new neurons in the cerebral cortex of stroke-prone spontaneously hypertensive rats after stroke.

    Science.gov (United States)

    Itoh, Tatsuki; Satou, Takao; Takemori, Kumiko; Hashimoto, Shigeo; Ito, Hiroyuki

    2010-05-01

    Stroke-prone spontaneously hypertensive rats (SHRSP) are the only animal model that suffers from spontaneous cerebral stroke. In this study, we investigated the appearance of neural stem cells (NSCs) and new neurons in the penumbra and the subventricular zone (SVZ) after cerebral stroke in SHRSP. SHRSP before cerebral stroke were intraperitoneally injected with 5-bromo-2'-deoxyuridine (BrdU). SHRSP were divided into acute and chronic phase groups after cerebral stroke. Brain sections from both groups were studied with cell-specific markers such as BrdU, a cell division and proliferation marker, sex-determining region Y-box 2, a marker of NSCs, nestin, an NSC and immature astrocyte marker, doublecortin, an immature new neuron marker, and neuron-specific nuclear protein, a marker of mature neurons. NSCs and new neurons appeared in the penumbra in the early stages after cerebral stroke, and these cells differentiated into mature neurons in the chronic phase. Furthermore, soon after being affected by a cerebral stroke, there were many new neurons and immature cells, which appear to be NSCs, in the ipsilateral SVZ. Immature cells and new neurons from the ipsilateral SVZ might migrate into the penumbra after cerebral stroke, and this is the first report of their observation after a spontaneous cerebral stroke.

  12. Ganoderma lucidum spore powder modulates Bcl-2 and Bax expression in the hippocampus and cerebral cortex, and improves learning and memory in pentylenetetrazole-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Shuang Zhao; Shengchang Zhang; Shuqiu Wang

    2011-01-01

    We studied the effects of Ganoderma lucidum spore powder on Bax and Bcl-2 expression and neuronal apoptosis in pentylenetetrazole-kindled epileptic rats. Sixty adult rats were randomly divided into a control group, an epileptic group (kindled) and three medication groups ( 150, 300,450 mg/kg given to kindled rats). Bax and Bcl-2 immunohistochemistry and TUNEL labeling show ed that the number of Bax- and TUNEL-positive cells in the hippocampus and cerebral cortex decreased significantly in the high-dose medication group, while the number of Bcl-2immunoreactive cells increased. The Morris water maze test showed that high-dose treatment significantly shortened escape latency and increased spatial probe trial performance. Our findings indicate that a high dose of Ganoderma lucidum spore powder upregulates the expressionof antiapoptotic Bcl-2 protein in the hippocampus and cerebral cortex, inhibits proapoptotic Bax expression, and decreases seizure-induced neuronal apoptosis. Further,Ganoderma lucidum appears to protect against epilepsy-related learning and memory impairments.

  13. 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

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    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.

  14. 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.

  15. Differential effects of organic and inorganic selenium compounds on adenosine deaminase activity and scavenger capacity in cerebral cortex slices of young rats.

    Science.gov (United States)

    Bitencourt, P E R; Bellé, L P; Bonfanti, G; Cargnelutti, L O; de Bona, K S; Silva, P S; Abdalla, F H; Zanette, R A; Guerra, R B; Funchal, C; Moretto, M B

    2013-09-01

    Selenium (Se) has anti-inflammatory and antioxidant properties and is necessary for the development and normal function of the central nervous system. This study was aimed to compare the in vitro effects of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one (C21H2HOSe; organoselenium) and sodium selenate (inorganic Se) on adenosine deaminase (ADA) activity, cell viability, lipid peroxidation, scavenger of nitric oxide (NO) and nonprotein thiols (NP-SH) content in the cerebral cortex slices of the young rats. A decrease in ADA activity was observed when the slices were exposed to organoselenium at the concentrations of 1, 10 and 30 µM. The same compound showed higher scavenger capacity of NO than the inorganic compound. Inorganic Se was able to protect against sodium nitroprusside-induced oxidative damage and increased the NP-SH content. Both the compounds displayed distinctive antioxidant capacities and were not cytotoxic for the cerebral cortex slices in the conditions tested. These findings are likely to be related to immunomodulatory and antioxidant properties of this compound.

  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.

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    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. Effects of movement training on synaptic interface structure in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere in cerebral infarction rats

    Institute of Scientific and Technical Information of China (English)

    Min Yang; Jiyan Cheng

    2008-01-01

    BACKGROUND: Movement is an effective way to provide sensory, movement and reflectivity afferent stimulation to the central nervous system. Movement plays an important role in functional recombination and compensation in the brain. OBJECTIVE: To observe movement training effects on texture parameters of synaptic interfaces in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere and on motor function in cerebral infarction rats. DESIGN, TIME AND SETTING: This neural morphology and pathology randomized controlled animal experiment was performed at the Center Laboratory, Affiliated Hospital of Luzhou Medical College, China from November 2004 to April 2005. MATERIALS: A total of 32 healthy male Wistar rats aged 8 weeks were equally and randomly assigned into model and movement training groups. METHODS: Rat models of right middle cerebral artery occlusion were established using the suture occlusion method in both groups. Rats in the movement training group underwent balance training, screen training, and rotating rod training starting on day 5 after surgery, for 40 minutes every day, 6 days per week, for 4 weeks. MAIN OUTCOME MEASURES: Texture parameters of synaptic interfaces were determined using a transmission electron microscope and image analyzer during week 5 following model induction. The following parameters were measured: synaptic cleft width; postsynaptic density thickness; synaptic interface curvature; and active zone length. Motor function was assessed using balance training, screen training, and rotating rod training. The lower score indicated a better motor function. RESULTS: The postsynaptic density thickness, synaptic interface curvature, and active zone length were significantly increased in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere of rats from the movement training group compared with the model group (P < 0.05 or 0.01). Curved synapses and perforated synapses were seen in the sensorimotor cortex

  18. In vitro evidence that D-serine disturbs the citric acid cycle through inhibition of citrate synthase activity in rat cerebral cortex.

    Science.gov (United States)

    Zanatta, Angela; Schuck, Patrícia Fernanda; Viegas, Carolina Maso; Knebel, Lisiane Aurélio; Busanello, Estela Natacha Brandt; Moura, Alana Pimentel; Wajner, Moacir

    2009-11-17

    The present work investigated the in vitro effects of D-serine (D-Ser) on important parameters of energy metabolism in cerebral cortex of young rats. The parameters analyzed were CO(2) generation from glucose and acetate, glucose uptake and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase and of creatine kinase and Na(+),K(+)-ATPase. Our results show that D-Ser significantly reduced CO(2) production from acetate, but not from glucose, reflecting an impairment of the citric acid cycle function. Furthermore, D-Ser did not affect glucose uptake. We also observed that the activity of the mitochondrial enzyme citrate synthase from mitochondrial preparations and purified citrate synthase was significantly inhibited by D-Ser, whereas the other activities of the citric acid cycle as well as the activities of complexes I-III, II-III, II and IV of the respiratory chain, creatine kinase and Na(+),K(+)-ATPase were not affected by this D-amino acid. We also found that L-serine did not affect citrate synthase activity from mitochondrial preparations and purified enzyme. The data indicate that D-Ser impairs the citric acid cycle activity via citrate synthase inhibition, therefore compromising energy metabolism production in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which D-Ser metabolism is impaired, with altered cerebral concentrations of this D-amino acid.

  19. 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

  20. siRNA-mediated silence of protease-activated receptor-1 minimizes ischemic injury of cerebral cortex through HSP70 and MAP2.

    Science.gov (United States)

    Zhang, Jun; Wang, Ying; Zhu, Ping; Wang, Xudong; Lv, Manhua; Feng, Honglin

    2012-09-15

    Cerebral ischemic stroke is a prevalent disease in senior individuals. The anticoagulation and thrombolysis to recover blood supply as well as the diminution of neural excitotoxicity to protect brain cells have not shown to fully improve stroke patients. The comprehensive mechanisms and medication specificity remain to be addressed. The silence of specific mRNAs by RNA interference provides revenues for such goals. We examined whether the silence of protease-activated receptor-1 (PAR-1) by siRNA protects brain tissues from ischemic injury. In three groups of Wistar rats, their lateral ventricles received the injections of lentiviral vectors carrying siRNA for PAR1, small RNA in mismatching PAR1 or saline. A week after the injections, these rats were treated by one side of middle cerebral artery occlusion (MCAO). The scores of neurological deficits, the volume of ischemic infarction and the expressions of PAR-1, HSP-70 and MAP-2 were measured in 24h of MCAO. Our results show that the silence of PAR-1 significantly reduces neurological deficits and infarction volume, as well as elevates HSP-70 and MAP-2 expressions. Thus, the knock-down of PAR1 minimizes the ischemic impairments of cerebral cortex via HSP70 and MAP-2 pathways. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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    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.

  2. Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex.

    Science.gov (United States)

    Wachi, Tomoka; Cornell, Brett; Marshall, Courtney; Zhukarev, Vladimir; Baas, Peter W; Toyo-oka, Kazuhito

    2016-06-01

    14-3-3 proteins are ubiquitously-expressed and multifunctional proteins. There are seven isoforms in mammals with a high level of homology, suggesting potential functional redundancy. We previously found that two of seven isoforms, 14-3-3epsilon and 14-3-3zeta, are important for brain development, in particular, radial migration of pyramidal neurons in the developing cerebral cortex. In this work, we analyzed the function of another isoform, the protein 14-3-3gamma, with respect to neuronal migration in the developing cortex. We found that in utero 14-3-3gamma-deficiency resulted in delays in neuronal migration as well as morphological defects. Migrating neurons deficient in 14-3-3gamma displayed a thicker leading process stem, and the basal ends of neurons were not able to reach the boundary between the cortical plate and the marginal zone. Consistent with the results obtained from in utero electroporation, time-lapse live imaging of brain slices revealed that the ablation of the 14-3-3gamma proteins in pyramidal neurons slowed down their migration. In addition, the 14-3-3gamma deficient neurons showed morphological abnormalities, including increased multipolar neurons with a thicker leading processes stem during migration. These results indicate that the 14-3-3gamma proteins play an important role in radial migration by regulating the morphology of migrating neurons in the cerebral cortex. The findings underscore the pathological phenotypes of brain development associated with the disruption of different 14-3-3 proteins and will advance the preclinical data regarding disorders caused by neuronal migration defects.

  3. Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.

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    Santosh Singh

    Full Text Available BACKGROUND AND PURPOSE: Liver dysfunction led hyperammonemia (HA causes a nervous system disorder; hepatic encephalopathy (HE. In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF. METHODS: ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS and glutaminase (GA, the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats. RESULTS: The ALF rats showed significantly increased levels of ammonia in the blood (HA but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats. CONCLUSION: ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.

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

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    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.

  5. 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.

  6. 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.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Benjamin eMeltzer

    2015-08-01

    Full Text Available 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 (EEG 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, nonsensical 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.

  9. Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: preferential expression by interneurons tangentially migrating from the ganglionic eminences.

    Science.gov (United States)

    Yau, Hau-Jie; Wang, Hsiao-Fang; Lai, Cary; Liu, Fu-Chin

    2003-03-01

    The receptor tyrosine kinases represent an important class of signal transduction molecules that have been shown to play critical roles in neural development. We report in the present study that the neuregulin receptor ErbB4 is preferentially expressed by interneurons that are migrating tangentially from the ventral to the dorsal rat telencephalon. ErbB4 immunoreactivity was detected in the medial ganglionic eminence as early as embryonic day (E) 13 at the inception of tangential migration. Prominent ErbB4-positive migratory streams consisting of cells double-labeled with ErbB4 and Dlx, a marker of tangentially migrating cells, were found to advance along the lower intermediate zone and the marginal zone from the ventrolateral to the dorsomedial cortex at E16-E18. After E20, the ErbB4-positive stream in the lower intermediate zone shifted towards the germinal zone and further extended via the cortex into the hippocampal primordium. ErbB4 was not expressed by Tbr1-positive glutamatergic projection neurons during development. ErbB4 was preferentially expressed by the majority of parvalbumin-positive interneurons and subsets of other GABAergic interneurons in the cerebral cortex and the hippocampus in adulthood. The early onset and preferential expression of ErbB4 in tangentially migrating interneurons suggests that neuregulin/ErbB4 signaling may regulate the development and function of telencephalic interneurons.

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

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    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

  11. 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.

  12. 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

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    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

  13. Morphological properties of nociceptive and non-nociceptive neurons in primary somatic cerebral cortex (SI) of cat

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    With the techniques of intracellular recording and labelling, we investigated pain sensation and modulation of the somatic cortical cortex at the neuron's level. After observing the evoked potentials from stimulating the saphenous nerves (SN) of 654 neurons in SI area of the cats, we labelled 30 of the neurons with Neurobiotin to preserve the distribution and the morphologic characteristics of the neurons in the cortex. Based on the tridimensional reconstruction in addition to the eletrophysiological functions, we found clear morphological distinctions between nociceptive and non-nociceptive neurons (P<0.01). This result provided new experimental material to illustrate the function of nociceptive neurons in somatosensory cortex (SI) and presented further evidence to support the "specificity theory" of pain sensation in terms of morphology.

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

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    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.

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

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    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.

  16. Characterization of the Fiber Connectivity Profile of the Cerebral Cortex in Schizotypal Personality Disorder: A Pilot Study.

    Science.gov (United States)

    Liu, Kai; Zhang, Teng; Zhang, Qing; Sun, Yueji; Wu, Jianlin; Lei, Yi; Chu, Winnie C W; Mok, Vincent C T; Wang, Defeng; Shi, Lin

    2016-01-01

    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 tractography. Diffusion and structural MR data were collected from 20 subjects with SPD (all males; age, 19.7 ± 0.9 years) and 18 healthy controls (all males; age, 20.3 ± 1.0 years). 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 BA 9 and BA 10) 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.

  17. 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.)

  18. Progressive loss of glutamic acid decarboxylase, parvalbumin, and calbindin D28K immunoreactive neurons in the cerebral cortex and hippocampus of adult rat with experimental hydrocephalus.

    Science.gov (United States)

    Tashiro, Y; Chakrabortty, S; Drake, J M; Hattori, T

    1997-02-01

    The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus. Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event

  19. Binding of transcription factors to Presenilin 1 and 2 promoter cis-acting elements varies during the development of mouse cerebral cortex.

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    Kumar, Ashish; Thakur, M K

    2016-08-15

    Previously, we reported differential expression of Presenilin (PS)1 and 2 and epigenetic modifications of their gene promoter in the cerebral cortex of mice during development. We identified the crucial role of DNA methylation and H3K9/14 acetylation in stage specific PS expression during brain development. Interestingly, we noted differential DNA methylation in putative binding sites of transcription factors considered pivotal for brain development. This prompted us to study the binding of transcription factors to cis-acting elements of PS1 and PS2 promoter in the cerebral cortex of mice during development. In-silico analysis revealed various cis-acting elements of PS1 and PS2 promoter and their putative transcription factors. We selected those cis-acting elements that were proven by wet lab experiments to interact with the transcription factors crucial for brain development. Electrophoretic mobility shift assay revealed that the binding of nuclear proteins to PS1 promoter cis-acting elements like HSF-1, Cdx1, Ets-1 and Sp1 significantly increased at embryonic day (E) 12.5, postnatal day (P) 45 and 20 weeks (w) as compared to P0. The binding pattern of these factors correlated well with the PS1 expression profile, indicating their cumulative influence on PS1 gene transcription. For PS2 promoter, the binding of Nkx2.2 and HFH-2 was high at prenatal stages (E12.5 and E18.5) while that of Cdx1 and NF-κB was maximum at postnatal stages (P45 and 20w). Taken together, our study shows that the binding of HSF-1, Cdx1, Ets-1 and Sp1 to PS1 promoter and that of Nkx2.2, HFH-2, Cdx1 and NF-κB to PS2 promoter regulate their differential expression during brain development.

  20. Early loss of the glutamate transporter splice-variant GLT-1v in rat cerebral cortex following lateral fluid-percussion injury.

    Science.gov (United States)

    Yi, Jae-Hyuk; Pow, David V; Hazell, Alan S

    2005-01-01

    Glutamate transporter proteins are essential for the control of interstitial glutamate levels, with an impairment of their function or levels being a major potential contributor to excitotoxicity. We have investigated the effects of lateral fluid percussion on the levels of the glutamate transporter proteins GLT-1alpha, its splice variant GLT-1v, GLAST, and EAAC1 in the rat in order to evaluate their pathogenetic role in this model of traumatic brain injury (TBI). Immunoblot analysis revealed neuronal loss in the cerebral cortex was accompanied by a 54% decrease in GLT-1v 6 h following the insult which progressed to an 83% loss of the transporter after 24 h. No changes in GLT-1alpha, GLAST, or EAAC1 were observed in this brain region at either time point. GLT-1v content was also decreased by 55% and 68% in the hippocampus and thalamus, respectively, at 6 h post-injury, but recovered fully after 24 h in both brain regions. In contrast, levels of GLT-1alpha were increased in the hippocampus at 6 h and 24 h post-TBI. These alterations in transporter protein content were also confirmed using immunohistochemical methods. Our results show for the first time a pattern of early, dynamic changes in the levels of GLT-1 transporter splice variants in different brain regions in this trauma model. In addition, correlation of GLT-1v levels with both neuronal cell loss and alpha-internexin content in the injured cortex suggests that loss of this novel glutamate transporter may be a key factor in determining cerebral vulnerability following this type of brain injury.

  1. DETERMINATION OF RAT CEREBRAL CORTEX FATTY ACID COMPOSITION AND CON-TENT BY GAS CHROMATOGRAPHY%气相色谱法分析大鼠大脑皮质脂肪酸组成及含量

    Institute of Scientific and Technical Information of China (English)

    石如玲; 张煜; 杨磊; 杨志军

    2011-01-01

    [Objective] To determine cerebral cortex fatty acid composition and content of rats. [Methods] Iipids were extracted from the cerebral cortex with methanol/dichloromethane and were methylesterified using methanol/acetyl chloride. Fatty acid methyl esters were then assayed by gas chromatography. [Results] Qualitative analysis results showed that there were 16 kinds of fatty acids in rat cerebral cortex, with major fatty acids as C18 : 0, followed by C16 : 0, C18 : 1, C20 : 4 and C22 6. The ratio of saturated fatty acids to unsaturated fatty acids in rat cerebral cortex was 1.22 : 1. [Conclusion] This study provided data on fatty acid composition and content of rat cerebral cortex, which laid the foundation for exploring the relation* ship between fatty acids and brain function.%[目的]对大鼠大脑皮质脂肪酸组成及含量进行分析测定.[方法]采用甲醇-二氯甲烷提取脑皮质总脂,用甲醇/乙酰氯法进行脂肪酸甲酯化,利用气相色谱法对脂肪酸组成及含量进行测定.[结果]定性分析结果表明大鼠脑皮质脂肪酸至少有16种,含量占优势的脂肪酸为C18:0、C16:0、C18:1、C20:4、C22:6;饱和与不饱和脂肪酸之比为1.22:1.[结论]该实验确定了大鼠大脑皮质脂肪酸的组成及含量,为进一步研究脂肪酸与脑功能打下了基础.

  2. 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

  3. 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.

  4. 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 produce...... neurovascular coupling after CSD. These findings suggest that CSD-induced increments in 20-HETE cause the reduction in CBF after CSD, and that the attenuation of stimulation-induced CBF responses after CSD has a different mechanism. We suggest that blockade of 20-HETE synthesis may be clinically relevant...

  5. Changes in cerebral activations during movement execution and imagery after parietal cortex TMS interleaved with 3T MRI

    NARCIS (Netherlands)

    de Vries, Paulien M.; de Jong, Bauke M.; Bohning, Daryl E.; Walker, John A.; George, Mark S.; Leenders, Klaus L.

    2009-01-01

    The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic

  6. Changes in cerebral activations during movement execution and imagery after parietal cortex TMS interleaved with 3T MRI

    NARCIS (Netherlands)

    de Vries, Paulien M.; de Jong, Bauke M.; Bohning, Daryl E.; Walker, John A.; George, Mark S.; Leenders, Klaus L.

    2009-01-01

    The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic resonan

  7. 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.

  8. Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex.

    Science.gov (United States)

    Alonso, David; Serrano, Julia; Rodríguez, Ignacio; Ruíz-Cabello, Jesús; Fernández, Ana Patricia; Encinas, Juan Manuel; Castro-Blanco, Susana; Bentura, María Luisa; Santacana, María; Richart, Ana; Fernández-Vizarra, Paula; Uttenthal, Lars Otto; Rodrigo, José

    2002-02-04

    Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS-immunoreactive band and calcium-dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV-V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium-independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham-perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L-NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia-reperfusion contributes to cerebral injury.

  9. Avalanche analysis from multi-electrode ensemble recordings in cat, monkey and human cerebral cortex during wakefulness and sleep.

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    Nima eDehghani

    2012-08-01

    Full Text Available Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep and REM sleep, using high-density electrode arrays in cat motor cortex (96 electrodes, monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes in epileptic patients. In neuronal avalanches defined from units (up to 160 single units, the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs and in particular LFP negative peaks (nLFPs among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and pre-motor cortices. In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.

  10. 实验性脑震荡大鼠脑皮质肿瘤坏死因子-α的表达%Changes of TNF-αexpression in cerebral cortex of experimental rats with pure cerebral concussion

    Institute of Scientific and Technical Information of China (English)

    严琦敏; 张排旗; 赵波; 张新宇; 付学锋

    2015-01-01

    目的:检测单纯性脑震荡( pure cerebral concussion,PCC)大鼠前额叶皮质( prefrontal cortex,PC)、颞叶皮质( temporal cortex,TC)和梨状皮质( piriform cortex,Pir)肿瘤坏死因子-α( TNF-α)的表达变化,探讨脑损伤早期TNF-α与病理变化的联系。方法采用“金属单摆闭合式脑损伤打击装置”在清醒状态下建立PCC模型大鼠,建立的模型大鼠按时间点随机分为1,12,24,48,72 h和7 d损伤组(n=6),另设正常对照组(n=6)。采用多克隆兔抗TNF-α免疫组织化学SP法观察PCC和正常对照大鼠PC、TC和Pir脑区TNF-α表达变化。结果早期PCC和正常对照大鼠TNF-α在PC、TC和Pir内表达均较弱。PCC大鼠的TNF-α阳性表达和阳性细胞数量逐渐增加,72 h达到峰值(P<0.05-0.01),7 d后有下降趋势,但仍高于正常组(P<0.05)。结论 PCC大鼠PC和TC区TNF-α表达可出现明显改变,提示TNF-α可能参与PCC的病理生理过程。%Objective To investigate the changes of tumor necrosis factor-α( TNF-α) in prefrontal cortex( PC) , temporal cortex( TC) and piriform cortex(Pir) after the pure cerebral concussion(PCC), and to explore its relationship with pathological changes in early stage of brain injury. Methods Under the consciousness condition, the PCC model rats were established by a metallic pendulum-striker concussive device. The model rats were randomly divided into 1,12,24,48,72 h and 7 d PCC groups(n=6 in each group), and six normal rats were chosen as control group. The distribution and changes of TNF-α expression in PC,TC and Pir were observed and compared by the immunohistochemistry with anti-TNF-αmonoclonal antibody between PCC groups and control group. Results The expression of TNF-α-immunoreactivity was weak in control group. The expression of TNF-α-immunoreactivity and the number of the TNF-α-immunopositive cells gradually increased from 1 h to 72 h in the PC and TC after the rat brain injury, and peaked at 72 h (P<0. 05 or 0. 01), and then

  11. Attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

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    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi (Osaka Univ. (Japan). Faculty of Medicine); Shiraishi, Junzo

    1982-06-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms.

  12. Prenatal genesis of layer II doublecortin expressing neurons in neonatal and young adult guinea pig cerebral cortex

    Directory of Open Access Journals (Sweden)

    Yan eYang

    2015-08-01

    Full Text Available Cells expressing doublecortin (DCX+ occur at cortical layer II, predominantly over the paleocortex in mice/rats, but also across the neocortex among larger mammals. Here we explored the time of origin of these cells in neonatal and two-month-old guinea pigs following prenatal BrdU pulse-chasing. In the neocortex, BrdU+ cells birth-dated at embryonic day 21 (E21, E28 and E35 laminated over the cortical plate with an inside-out order. In the piriform cortex, cells generated at E21 and E28 occurred with a greater density in layer II than III. Many cells were generated at later time points until birth, occurring in the cortex without a laminar preference. DCX+ cells in the neocortex and piriform cortex partially co-colocalized with BrdU (up to 7.5% in the newborns after pulse-chasing from E21 to E49 and in the 2 month-old animals after pulse-chasing from E28 to E60/61, with higher rates seen among the E21-E35 groups. Together, layer II DCX+ cells in neonatal and young adult guinea pigs may be produced over a wide prenatal time window, but mainly during the early phases of corticogenesis. Our data also show an earlier establishment of the basic lamination in the piriform relative to neocortical areas in guinea pigs.

  13. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain Efectos moduladores de la N-acetilcisteína sobre la corteza cerebral y las regiones cerebelosas sobre la del cerebro senescente de rata

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    S. Singh Kanwar

    2007-02-01

    Full Text Available Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since Nacetylcysteine (NAC has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH content along with the activities of superoxide dismutase (SOD and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months and older (14 months female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day, lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older rats. Further, in the younger rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.El estrés oxidativo se ha implicado en el envejecimiento cerebral y en los trastornos neurodegenerativos asociados con la edad. Puesto que recientemente se ha demostrado que la N-acetilcisteína (NAC previene el daño oxidativo en el cerebro senescente, hemos explorado los efectos de este antioxidante tiólico sobre

  14. Nerve growth factor downregulates c-jun mRNA and Caspase-3 in striate cortex of rats after transient global cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Dacheng Jin; Tiemin Wang; Xiubin Fang

    2006-01-01

    BACKGROUND: Immediate early gene (LEG) c-jun is a sensitive marker for functional status of nerve cells.Caspase-3 is a cysteine protease,which is a critical regulator of apoptosis. The effect of exogenous nerve growth factor (NGF) on the expression of c-jun Mrna and Caspase-3 protein in striate cortex of rats with transient global cerebral ischemia/reperfusion (IR) is unclear.OBJECTIVE: To study the protective effect of exogenous NGF on the brain of rats with transient global cerebral IR and its effecting pathway by observing the expression of c-jun Mrna and Caspase-3 protein.DESIGN: Randomized controlled animal trial.SETTING: Department of Neural Anatomy, Institute of Brain,China Medical University.MATERTALS:Eighteen healthy male SD rats of clean grade, aged 1 to 3 months, with body mass of 250 to 300 g, were involved in this study. NGF was provided by Dalian Svate Pharmaceutical Co.,Ltd, c-jun in situ hybridization detection kit, Caspase-3 antibody and SABC kit were purchased from Boster Biotechnology Co. ,Ltd.METHODS: This trial was carried out in the Department of Neural Anatomy, Institute of Brain, China Medical University during September 2003 to April 2005. ①Experimental animals were randomized into three groups with 6 in each: sham-operation group,IR group and NGF group. ②After the rats were anesthetized,the bilateral common carotid arteries and right external carotid arteries of rats were bluntly dissected and bilateral common carotid arteries were clamped for 30 minutes with bulldog clamps. Reperfusion began after buldog clamps were removed. Normal saline of 1mL and NGF (1×106 U/L) of 1 Ml was injected into the common carotid artery of rats via right external carotid arteries in the IR group and NGF group respectively.The injection was conducted within 30 minutes, and then the right external carotid arteries were ligated. In the sham-operation group, occlusion of bilateral common carotid arteries and administration of drugs were phosphate buffer

  15. [Pharmacological correction of neuronal damage in sensomotor zone of frontal cortex under conditions of experimental cerebral blood flow pathology].

    Science.gov (United States)

    Gorbacheva, S V; Belenichev, I F; Dunaev, V V; Bukhtiiarova, N V

    2007-01-01

    The administration of thiotriazoline, emoxypine and magnelong (a combined glycine-magnesium preparation) to animals with acute cerebral circulatory insufficiency showed significant neuroprotective effect in both acute and late ischemic periods, as indicated by the indices of cell density and number and the characteristics of apoptic and destructed neurons approaching those in the group of intact rats. Pyracetam showed cerebroprotective effect only in late ischemic period. Magnelong exhibited the most significant neuroprotective effect, maintaining cell density on the intact control level and reducing the number of apoptotic and destructed neurons.

  16. Selective loss of parvalbumin-positive GABAergic interneurons in the cerebral cortex of maternally stressed Gad1-heterozygous mouse offspring.

    Science.gov (United States)

    Uchida, T; Furukawa, T; Iwata, S; Yanagawa, Y; Fukuda, A

    2014-03-11

    Exposure to maternal stress (MS) and mutations in GAD1, which encodes the γ-aminobutyric acid (GABA) synthesizing enzyme glutamate decarboxylase (GAD) 67, are both risk factors for psychiatric disorders. However, the relationship between these risk factors remains unclear. Interestingly, the critical period of MS for psychiatric disorders in offspring corresponds to the period of GABAergic neuron neurogenesis and migration in the fetal brain, that is, in the late stage of gestation. Indeed, decrement of parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has often been observed in schizophrenia patients. In the present study, we used GAD67-green fluorescent protein (GFP) knock-in mice (that is, mice in which the Gad1 gene is heterozygously deleted; GAD67(+/GFP)) that underwent prenatal stress from embryonic day 15.0 to 17.5 and monitored PV-positive GABAergic neurons to address the interaction between Gad1 disruption and stress. Administration of 5-bromo-2-deoxyuridine revealed that neurogenesis of GFP-positive GABAergic neurons, but not cortical plate cells, was significantly diminished in fetal brains during MS. Differential expression of glucocorticoid receptors by different progenitor cell types may underlie this differential outcome. Postnatally, the density of PV-positive, but not PV-negative, GABAergic neurons was significantly decreased in the mPFC, HIP and somatosensory cortex but not in the motor cortex of GAD67(+/GFP) mice. By contrast, these findings were not observed in wild-type (GAD67(+/+)) offspring. These results suggest that prenatal stress, in addition to heterozygous deletion of Gad1, could specifically disturb the proliferation of neurons destined to be PV-positive GABAergic interneurons.

  17. A Cognição Social e o Córtex Cerebral Social Cognition and the Brain Cortex

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    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

  18. Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

    Science.gov (United States)

    Leontiev, Oleg; Buracas, Giedrius T; Liang, Christine; Ances, Beau M; Perthen, Joanna E; Shmuel, Amir; Buxton, Richard B

    2013-03-01

    The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration.

  19. Diffusion-Weighted MRI in Creutzfeldt-Jakob Disease: Focus on the Cerebral Cortex and Chronologic Change

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun; Song, Chang Joon; Lee, In Ho [Chungnam National University, Daejeon (Korea, Republic of); Yu, In Kyu [Eulji University Hospital, Seoul (Korea, Republic of); Choi, See Sung [Wonkwang University Hospital, Iksan (Korea, Republic of)

    2010-08-15

    To evaluate high cortical signal intensity and chronologic changes for diffusion-weighted MR imaging (DWI) in sporadic Creutzfeldt-Jakob disease. We retrospectively analyzed the DWI results of 16 patients with probable CJD (according to WHO criteria) and evaluated the distribution, extent and bilaterality of the lesions in the cortex, basal ganglia and thalamus. We also reviewed the chronologic changes of the lesions by evaluating the followup MR examination results in 8 of 16 patients. Cortical abnormalities were present in 15 (94%) of 16 patients. Isolated cortical involvement was present in 6 patients (40%), while the combined involvement of the cortex and basal ganglia was present in 9 patients (60%). The distribution of the lesions was bilateral in 12 patients and predominantly on the right side in 8 patients. Upon follow-up MR imaging, the cortical lesions showed progress in terms of extent and signal intensity. Basal ganglia abnormalities were present in 9 of 15 patients. Moreover, 4 of 6 patients who had no abnormal signal intensity in the basal ganglia on the initial MR imaging results, showed abnormally high signal intensity upon follow-up MR imaging. The characteristically high cortical signal intensities on DWI in an elderly patient with rapidly progressive dementia should point to the diagnosis of early phase CJD and might be useful for the differential diagnosis.

  20. 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.

  1. Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

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    Liliana Germán-Castelán

    2014-01-01

    Full Text Available Progesterone (P4 promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL, P4 (1 mg, RU486 (5 mg, or P4 + RU486 (1 mg and 5 mg, resp. for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor.

  2. Spatial frequency-based analysis of mean red blood cell speed in single microvessels: investigation of microvascular perfusion in rat cerebral cortex.

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    Joonas Autio

    Full Text Available BACKGROUND: Our previous study has shown that prenatal exposure to X-ray irradiation causes cerebral hypo-perfusion during the postnatal development of central nervous system (CNS. However, the source of the hypo-perfusion and its impact on the CNS development remains unclear. The present study developed an automatic analysis method to determine the mean red blood cell (RBC speed through single microvessels imaged with two-photon microscopy in the cerebral cortex of rats prenatally exposed to X-ray irradiation (1.5 Gy. METHODOLOGY/PRINCIPAL FINDINGS: We obtained a mean RBC speed (0.9±0.6 mm/sec that ranged from 0.2 to 4.4 mm/sec from 121 vessels in the radiation-exposed rats, which was about 40% lower than that of normal rats that were not exposed. These results were then compared with the conventional method for monitoring microvascular perfusion using the arteriovenous transit time (AVTT determined by tracking fluorescent markers. A significant increase in the AVTT was observed in the exposed rats (1.9±0.6 sec as compared to the age-matched non-exposed rats (1.2±0.3 sec. The results indicate that parenchyma capillary blood velocity in the exposed rats was approximately 37% lower than in non-exposed rats. CONCLUSIONS/SIGNIFICANCE: The algorithm presented is simple and robust relative to monitoring individual RBC speeds, which is superior in terms of noise tolerance and computation time. The demonstrative results show that the method developed in this study for determining the mean RBC speed in the spatial frequency domain was consistent with the conventional transit time method.

  3. Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study.

    Science.gov (United States)

    Nyúl-Tóth, Ádám; Suciu, Maria; Molnár, Judit; Fazakas, Csilla; Haskó, János; Herman, Hildegard; Farkas, Attila E; Kaszaki, József; Hermenean, Anca; Wilhelm, Imola; Krizbai, István A

    2016-06-01

    The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.

  4. Protection of Cactus Polysaccharide against H2O2-induced damage in the rat cerebral cortex and hippocampus Differences In time of administration

    Institute of Scientific and Technical Information of China (English)

    Xianju Huang; Qin Li; Lianjun Guo; Zankai Yan

    2008-01-01

    BACKGROUND: Pharmacological research has shown that cactus polysaccharide (CP) has anti-oxidant, anti-inflammatory, antitumor, anti-aging, and immune-stimulating activities. It may also provide protective effects against oxidative stress injuries in the rat brain.OBJECTIVE: To validate the effects of CP on H2O2-induced oxidative stress injuries in the ratcerebral cortex and hippocampal slices 30 minutes prior to injury, as well as 30 minutes and 2.5 hours after injury.DESIGN: A randomized controlled experiment.SETTINGS: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology; Department of Pharmacology, College of Medical Science, Yangtze University.MATERIALS: A total of 50 male Sprague Dawley (SD) rats, normal grade and weighing 200-300 g, were provided by the Laboratory Animal Center of Tongji Medical College, Huazhong University of Science and Technology. The protocol was performed in accordance with ethical guidelines for the use and care of ani-mals. Cactus polysaccharide, a dried needle crystal, was extracted from Opuntia milpa alta at the Chemistry and Environment Engineering School of Yangtze University. The following chemicals and instruments were used: 2,3,5-triphenyl tetrazolium chloride (Sigma, St Louis, Missouri, USA); lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH), and total antioxidant competence (T-AOC) assays (Jiancheng-Bioeng Institute, Nanjing); McIllwain tissue chopper (Mickle Laboratory Engineering, USA); and ELISA reader and Magellan software (TECAN, Austria).METHODS: This experiment was performed at the Department of Pharmacology, Medical College of Yangtze University, between March and June 2006. All rats were sacrificed after anesthesia. The cerebral cortex and hippocampus were dissected. Several cerebral cortex and hippocampus slices were selected as controls, while other sections were co-incubated with H2O2 for 30 minutes to induce an oxidative stress injury. The

  5. Amylin Treatment Reduces Neuroinflammation and Ameliorates Abnormal Patterns of Gene Expression in the Cerebral Cortex of an Alzheimer’s Disease Mouse Model

    Science.gov (United States)

    Wang, Erming; Zhu, Haihao; Wang, Xiaofan; Gower, Adam C.; Wallack, Max; Blusztajn, Jan Krzysztof; Kowall, Neil; Qiu, Wei Qiao

    2017-01-01

    Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer’s disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice. Mechanistic studies indicated the protective effect of amylin required interaction with its cognate receptor because silencing the amylin receptor expression blocked the amylin effect on Cd68 in microglia. Using weighted gene co-expression network analysis, we discovered that amylin treatment influenced two gene modules linked with amyloid pathology: 1) a module related to proinflammation and transport/vesicle process that included a hub gene of Cd68, and 2) a module related to mitochondria function that included a hub gene of Atp5b. Amylin treatment restored the expression of most genes in the APP cortex toward levels observed in the wild-type (WT) cortex in these two modules including Cd68 and Atp5b. Using a human dataset, we found that the expression levels of Cd68 and Atp5b were significantly correlated with the neurofibrillary tangle burden in the AD brain and with their cognition. These data suggest that amylin acts on the pathological cascade in animal models of AD, and further supports the therapeutic potential of amylin-type peptides for AD. PMID:27911303

  6. Hyperthermia-induced seizures alter adenosine A1 and A2A receptors and 5'-nucleotidase activity in rat cerebral cortex.

    Science.gov (United States)

    León-Navarro, David Agustín; Albasanz, José L; Martín, Mairena

    2015-08-01

    Febrile seizure is one of the most common convulsive disorders in children. The neuromodulator adenosine exerts anticonvulsant actions through binding adenosine receptors. Here, the impact of hyperthermia-induced seizures on adenosine A1 and A2A receptors and 5'-nucleotidase activity has been studied at different periods in the cerebral cortical area by using radioligand binding, real-time PCR, and 5'-nucleotidase activity assays. Hyperthermic seizures were induced in 13-day-old rats using a warmed air stream from a hair dryer. Neonates exhibited rearing and falling over associated with hindlimb clonus seizures (stage 5 on Racine scale criteria) after hyperthermic induction. A significant increase in A1 receptor density was observed using [(3) H]DPCPX as radioligand, and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density was detected, using [(3) H]ZM241385 as radioligand, 48 h after hyperthermia-evoked convulsions. These short-term changes in A1 and A2A receptors were also accompanied by a loss of 5'-nucleotidase activity. No significant variations either in A1 or A2A receptor density or 5'-nucleotidase were observed 5 and 20 days after hyperthermic seizures. Taken together, both regulation of A1 and A2A receptors and loss of 5'-nucleotidase in the cerebral cortex suggest the existence of a neuroprotective mechanism against seizures. Febrile seizure is one of the most common convulsive disorders in children. The consequences of hyperthermia-induced seizures (animal model of febrile seizures) on adenosine A1 and A2A receptors and 5'-nucleotidase activity have been studied at different periods in cerebral cortical area. A significant increase in A1 receptor density and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density and 5'-nucleotidase activity was detected 48 h after convulsions evoked by hyperthermia

  7. 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...

  8. 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

    . 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......-band waveforms from AC-coupled recordings. We constructed digital filters that reproduced the phase and amplitude distortions introduced by specific AC-coupled amplifiers and, based on this characterization, derived digital inverse filters to remove these distortions from ECoG recordings. Performance...... of the inverse filter was validated by its ability to recover both simulated and real low-frequency input test signals. The inverse filter was then applied to AC-coupled ECoG recordings from five patients who underwent invasive monitoring after aneurysmal subarachnoid hemorrhage. For 117 SPCs, the inverse filter...

  9. Recovery of slow potentials in AC-coupled electrocorticography: application to spreading depolarizations in rat and human cerebral cortex.

    Science.gov (United States)

    Hartings, Jed A; Watanabe, Tomas; Dreier, Jens P; Major, Sebastian; Vendelbo, Leif; Fabricius, Martin

    2009-10-01

    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-band waveforms from AC-coupled recordings. We constructed digital filters that reproduced the phase and amplitude distortions introduced by specific AC-coupled amplifiers and, based on this characterization, derived digital inverse filters to remove these distortions from ECoG recordings. Performance of the inverse filter was validated by its ability to recover both simulated and real low-frequency input test signals. The inverse filter was then applied to AC-coupled ECoG recordings from five patients who underwent invasive monitoring after aneurysmal subarachnoid hemorrhage. For 117 SPCs, the inverse filter recovered full-band waveforms with morphologic characteristics typical of the negative DC shifts recorded in animals. Compared with those recorded in the rat cortex with the same analog and digital methods, the negative DC shifts of human depolarizations had significantly greater durations (1:47 vs. 0:45 min:sec) and peak-to-peak amplitudes (10.1 vs. 4.2 mV). The inverse filter thus permits the study of spreading depolarizations in humans, using the same assessment of full-band DC potentials as that in animals, and suggests a particular solution for recovery of biosignals recorded with frequency-limited amplifiers.

  10. Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

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    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.

  11. 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

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    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.

  12. Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study

    Science.gov (United States)

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

    2014-01-01

    This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse. PMID:25550769

  13. The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome

    Science.gov (United States)

    Li, Shan Shan; Qu, Zhengdong; Haas, Matilda; Ngo, Linh; Heo, You Jeong; Kang, Hyo Jung; Britto, Joanne Maria; Cullen, Hayley Daniella; Vanyai, Hannah Kate; Tan, Seong-Seng; Chan-Ling, Tailoi; Gunnersen, Jenny Margaret; Heng, Julian Ik-Tsen

    2016-01-01

    Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate β-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter β-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome. PMID:27404227

  14. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.

    Science.gov (United States)

    Sumathi, Thangarajan; Shobana, Chandrasekar; Thangarajeswari, Mohan; Usha, Ramakrishnan

    2015-01-01

    L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

  15. Inhibition of sPLA₂-IIA prevents LPS-induced neuroinflammation by suppressing ERK1/2-cPLA₂α pathway in mice cerebral cortex.

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    Yanxiao Xiang

    Full Text Available Neuroinflammation is involved in various central nervous system (CNS disorders, including brain infections, ischemia, trauma, stroke, and degenerative CNS diseases. In the CNS inflammation, secretory phospholipase A₂-IIA (sPLA₂-IIA acts as a mediator, resulting in the generation of the precursors of pro-inflammatory lipid mediators, such as prostaglandins (PGs and leukotrienes (LTs. However, the role of sPLA₂-IIA in neuroinflammation is more complicated and remains unclear yet. In the present study, we investigated the effect of sPLA₂-IIA inhibition by specific inhibitor SC-215 on the inflammation in LPS-induced mice cerebral cortex and primary astrocytes. Our results showed that the inhibition of sPLA₂-IIA alleviated the release of PGE₂ by suppressing the activation of ERK1/2, cPLA₂α, COX-2 and mPGES-1. These findings demonstrated that sPLA₂-IIA showed the potential to regulate the neuroinflammation in vivo and in vitro, indicating that sPLA₂-IIA might be a novel target for the treatment of acute neuroinflammation.

  16. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

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    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.

  17. Perinatal exposure to PTU decreases expression of Arc, Homer 1, Egr 1 and Kcna 1 in the rat cerebral cortex and hippocampus.

    Science.gov (United States)

    Kobayashi, Kumiko; Akune, Haruyo; Sumida, Kayo; Saito, Koichi; Yoshioka, Takafumi; Tsuji, Ryozo

    2009-04-06

    Environmental chemicals have a potential impact on neuronal development and children's health. The current developmental neurotoxicity (DNT) guideline studies to assess their underlying risk are costly and time-consuming; therefore the more efficient protocol for DNT test is needed. Hypothyroidism in rats induced by perinatal exposure to propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, offers an advantageous model of developmental neurotoxicity (DNT). Understanding the associated alterations in gene expression in brain is a key to elucidate mechanisms and find appropriate molecular markers. The purpose of the present study was to identify PTU treatment-affected transcriptomes in the rat cerebral cortex and the hippocampus using DNA microarrays, and to specify candidate genes linked to DNT. We used an approximately 9000 probe microarray to examine differentially expressed genes between PTU-dosed and vehicle-dosed rats at postnatal days 4, 14, 22 and 70. Expression of immediate early genes (IEGs) such as activity-regulated cytoskeleton-associated protein (Arc), Homer 1, early growth response 1 (Egr 1), myelin-associated genes such as myelin-associated oligodendrocytic basic protein (MOBP), myelin basic protein (MBP) and proteolipid protein (PLP) and Kcna1 was apparently affected by perinatal administration of PTU. The results suggest that the alterations may be responsible for the detrimental effects caused by PTU treatment on the nervous system.

  18. In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

    Directory of Open Access Journals (Sweden)

    L.M. Zanatta

    2001-10-01

    Full Text Available The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10% in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27% in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group. When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80% occurring at 0.5 mM. We suggest that a imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.

  19. Effects of systemic administration of the essential oil of bergamot (BEO) on gross behaviour and EEG power spectra recorded from the rat hippocampus and cerebral cortex.

    Science.gov (United States)

    Rombolà, Laura; Corasaniti, Maria Tiziana; Rotiroti, Domenicantonio; Tassorelli, Cristina; Sakurada, Shinobu; Bagetta, G; Morrone, Luigi Antonio

    2009-01-01

    Bergamot (Citrus bergamia Risso et Poiteau) is a citrus fruit growing almost exclusively in the South of Italy. Its essential oil is obtained by cold pressing of the epicarp and, partly, of the mesocarp of the fresh fruit. Although this phytocomplex has been used for centuries, reputedly effectively, as a traditional medicine, there is very little verified scientific evidence to support this use. This paper reports original data on the systemic effects of the essential oil of bergamot (BEO) on gross behaviour and EEG activity recorded from the hippocampus and cerebral cortex of the rat. The Fast Fourier Transformation (FFT) was used to analyse and quantify the energy in single frequency bands of the EEG spectrum. The results obtained indicate that systemic administration of increasing volumes of BEO produces dose-dependent increases in locomotor and exploratory activity that correlate with a predominant increase in the energy in the faster frequency bands of the EEG spectrum. These data contribute to our understanding of the neurobiological profile of BEO.

  20. Leucine-rich α2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex.

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    Masakazu Miyajima

    Full Text Available Leucine-rich α2-glycoprotein (LRG is a protein induced by inflammation. It contains a leucine-rich repeat (LRR structure and easily binds with other molecules. However, the function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we measured human LRG (hLRG concentration in the cerebrospinal fluid (CSF and observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic (Tg mice that over-expressed mouse LRG (mLRG in the brain to examine the effects of mLRG accumulation. Finally, we examined protein-protein interactions using a protein microarray method to screen proteins with a high affinity for hLRG. The CSF concentration of hLRG increases with age and is significantly higher in patients with Parkinson's disease with dementia (PDD and progressive supranuclear palsy (PSP than in healthy elderly people, idiopathic normal pressure hydrocephalus (iNPH patients, and individuals with Alzheimer's disease (AD. Tg mice exhibited neuronal degeneration and neuronal decline. Accumulation of LRG in the brains of PDD and PSP patients is not a primary etiological factor, but it is thought to be one of the causes of neurodegeneration. It is anticipated that hLRG CSF levels will be a useful biomarker for the early diagnosis of PDD and PSP.

  1. The Role of Neonatal Carnitine Palmitoyl Transferase Deficiency Type II on Proliferation of Neuronal Progenitor Cells and Layering of the Cerebral Cortex in the Developing Brain

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    Heepeel Chang

    2007-06-01

    Full Text Available Neonatal Carnitine Palmitoyl Transferase Deficiency Type II, characterized by the absence of CPT II enzyme, is one of the lethal disorders of mitochondrial fatty acid oxidation. CPT II regulates the conversion of long chain fatty acids, so that its product, acyl-CoA esters, can enter the Krebs cycle and generate energy. Neonatal mutations of CPT II lead to severe disruption of the metabolism of long-chain fatty acids and result in dysmorphic features, cystic renal dysplasia, and neuronal migration defects. Examination of the brain from an approximately 15-week gestation human fetus with CPT II deficiency revealed premature formation of cerebral cortical gyri and sulci and significantly lower levels of neuronal cell proliferation in the ventricular and subventricular zones as compared to the reference cases. We used immunohistochemical markers to further characterize the effect of CPT II deficiency on progenitor cell proliferation and layering of neurons. These studies demonstrated a premature generation of layer 5 cortical neurons. In addition, both the total number and percentage of progenitor cells proliferating in the ventricular zone were markedly reduced in the CPT II case in comparison to a reference case. Our results indicate that CPT II deficiency alters the normal program of cellular proliferation and differentiation in the cortex, with early differentiation of progenitor cells associated with premature cortical maturation.

  2. 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

  3. Neurofisiologia e plasticidade no córtex cerebral pela estimulação magnética transcraniana repetitiva Plasticity of the human cerebral cortex as revealed by transcranial magnetic stimulation

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    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.

  4. Dor central devida a compressão do cortex parietal por tumor cerebral: relato de dois casos Central pain from cerebral cortical parietal tumors: report of two cases

    Directory of Open Access Journals (Sweden)

    Edson José Amâncio

    2002-06-01

    Full Text Available Dor central produzida por tumores cerebrais é considerada rara pela maioria dos autores. Os poucos casos descritos na literatura fazem referência à dor central provocada pela presença de lesões expansivas acometendo o córtex parietal contralateral. Nem mesmo os tumores talâmicos costumam produzir dor central. Apresentamos dois casos de dor central associada a lesões expansivas que acometeram o córtex parietal, 1 astrocitoma low grade e 1 meningioma. Em ambos houve alívio da dor após a remoção cirúrgica das lesões.Central pain derived from cerebral tumors is considered rare by most authors. The few cases described in literature refer to central pain caused by expansive lesions in the contralatral parietal cortex. Usually, not even thalamic tumors cause central pain. We describe two cases of central pain related to expansive lesions in the parietal cortical region -- a low grade astrocytoma and a meningioma. Both patients reported pain relief after lesions were removed by surgery.

  5. Deciphering the neuronal circuitry controlling local blood flow in the cerebral cortex with optogenetics in PV::Cre transgenic mice

    Directory of Open Access Journals (Sweden)

    Alan eUrban

    2012-06-01

    Full Text Available 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 (fMRI 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, 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.

  6. Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.

    Science.gov (United States)

    Thomas, Roshni Baby; Joy, Shilpa; Ajayan, M S; Paulose, C S

    2013-11-01

    Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

  7. 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.

  8. Experimental study on alteration of adrenergic receptors activity in neuronal membranes protein of cerebral cortex following brain trauma in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-wei; XU Ru-xiang; QI Yi-long; CHEN Chang-cai

    2001-01-01

    Objective: To define the course of changes taken by α1 and β adrenergic receptors (AR) activity after traumatic brain injury (TBI) and explore the approach for secondary brain injury (SBI) management. Methods: The neuronal membrane protein of cortex were extracted from the rats subject to traumatic brain injury, and the changes of α1- and β-AR activities in the neuronal membranes were examined by radio ligand binding assay (RLBA). Results: α1- and β-AR activities underwent obvious changes, reaching their peak values at 24 h after TBI. α1-AR binding density (Bmax) reduced by 22.6%while the ligand affinity increased by 66.7%, and for β-AR, however, Bmax increased by 116.9% and the ligand affinity reduced by 50.7%. Their antagonists could counteract the changes ofα1- and β-AR activity. Conclusion: The patterns of changes varies between α1- and β-AR activity after TBI, suggesting their different roles in the neuronal membranes after brain trauma, and timely administration of AR antagonists is potentially beneficial in TBI management.

  9. A 3D-investigation shows that angiogenesis in primate cerebral cortex mainly occurs at capillary level.

    Science.gov (United States)

    Risser, Laurent; Plouraboué, Franck; Cloetens, Peter; Fonta, Caroline

    2009-04-01

    This paper describes the use of a new 3D high-resolution imaging technique dedicated to functional vessels for a systematic quantitative study of angiogenesis in the primate cortex. We present a new method which permits, using synchrotron X-ray micro-tomography imaging, the identification of micro-vascular components as well as their automatic numerical digitalization and extraction from very large 3D image analysis and post-treatments. This method is used to analyze various levels of micro-vascular organization and their postnatal modifications. Comparing newborn- and adult marmosets, we found an increase in vascular volume (270%), exchange surface (260%) and vessel length (290%) associated to a decrease in distances between vessel and tissue (32%). The increase in relative vascular volumes between the two ages, examined through the whole cortical depth, has been found to be mainly sustained by events occurring at the capillary level, and only marginally at the perforating vessel level. This work shows that the postnatal cortical maturation classically described in terms of synaptogenesis, gliogenesis and connectivity plasticity is accompanied by an intensive remodeling of micro-vascular patterns.

  10. Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Potashner, S.J.; Gerard, D.

    1983-06-01

    A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). Baclofen (4 X 10(-6)M), an antispastic drug, and pentobarbital (10(-4)M), an anesthetic agent, each inhibited the electrically evoked release of D-ASP and prevented the enhancement of the release above control levels usually produced by 10(-4)M kainic acid. It is proposed that 10(-5) and 10(-4)M kainic acid may enhance the synaptic release of L-GLU and L-ASP from neurons which use these amino acids as transmitters. This action is prevented by baclofen and pentobarbital. In view of the possibility that cell death in Huntington's disease could involve excessive depolarization of striatal and other cells by glutamate, baclofen might be effective in delaying the loss of neurons associated with this condition.

  11. Widespread alterations in the synaptic proteome of the adolescent cerebral cortex following prenatal immune activation in rats.

    Science.gov (United States)

    Györffy, Balázs A; Gulyássy, Péter; Gellén, Barbara; Völgyi, Katalin; Madarasi, Dóra; Kis, Viktor; Ozohanics, Olivér; Papp, Ildikó; Kovács, Péter; Lubec, Gert; Dobolyi, Árpád; Kardos, József; Drahos, László; Juhász, Gábor; Kékesi, Katalin A

    2016-08-01

    An increasing number of studies have revealed associations between pre- and perinatal immune activation and the development of schizophrenia and autism spectrum disorders (ASDs). Accordingly, neuroimmune crosstalk has a considerably large impact on brain development during early ontogenesis. While a plethora of heterogeneous abnormalities have already been described in established maternal immune activation (MIA) rodent and primate animal models, which highly correlate to those found in human diseases, the underlying molecular background remains obscure. In the current study, we describe the long-term effects of MIA on the neocortical pre- and postsynaptic proteome of adolescent rat offspring in detail. Molecular differences were revealed in sub-synaptic fractions, which were first thoroughly characterized using independent methods. The widespread proteomic examination of cortical samples from offspring exposed to maternal lipopolysaccharide administration at embryonic day 13.5 was conducted via combinations of different gel-based proteomic techniques and tandem mass spectrometry. Our experimentally validated proteomic data revealed more pre- than postsynaptic protein level changes in the offspring. The results propose the relevance of altered synaptic vesicle recycling, cytoskeletal structure and energy metabolism in the presynaptic region in addition to alterations in vesicle trafficking, the cytoskeleton and signal transduction in the postsynaptic compartment in MIA offspring. Differing levels of the prominent signaling regulator molecule calcium/calmodulin-dependent protein kinase II in the postsynapse was validated and identified specifically in the prefrontal cortex. Finally, several potential common molecular regulators of these altered proteins, which are already known to be implicated in schizophrenia and ASD, were identified and assessed. In summary, unexpectedly widespread changes in the synaptic molecular machinery in MIA rats were demonstrated which

  12. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  13. 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.

  14. Effects of salvianolic acid B on proliferation, neurite outgrowth and differentiation of neural stem cells derived from the cerebral cortex of embryonic mice

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Salvianolic acid B is isolated from Salvia miltiorrhiza,the root of which is widely used as a traditional Chinese medicine to treat stroke.However,little is known about how salvianolic acid B influences growth characteristics of neural stem cells (NSCs).The purpose of the present study was to evaluate the effects of salvianolic acid B on proliferation,neurite outgrowth and differentiation of NSCs derived from the cerebral cortex of embryonic mice using MTT,flow cytometry,immunofluorescence and RT-PCR.It was found that 20 μg mL·1 and 40 μg mL·1 salvianolic acid B had similar effects on proliferation of NSCs,and a suitable concentration of salvianolic acid B increased the number of NSCs and their derivative neurospheres.The growth-promoting activity of salvianolic acid B was dependent on and associated with an accumulation in the G2/S-phase cell population.Salvianolic acid B also promoted the neurite outgrowth of NSCs and their differentiation into neurons.The mRNA for tau,GFAP and nestin were present in differentiating neurospheres induced by salvianolic acid B.However,high-level expression of tau mRNA and low-level expression of GFAP mRNA was detected in differentiated cells,in contrast to the control conditions.This collective evidence indicates that exogenous salvianolic acid B is capable of promoting proliferation of neurospheres and differentiation towards the neuronal lineage in vitro and may act in the proliferation of NSCs and may promote NSC differentiation into neuronal cells.

  15. Lack of excitatory amino acid-induced effects on calcium fluxes measured with sup 45 Ca sup 2+ in rat cerebral cortex synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Simonato, M.; Jope, R.S.; Bianchi, C.; Beani, L. (Univ. of Ferrara (Italy))

    1989-07-01

    Ca{sup 2+} uptake was measured in purified rat cerebral cortex synaptosomes (P3 pellets) using {sup 45}Ca{sup 2+} as a tracer. Ca{sup 2+} influx increased in time, and with an increase in external K+ concentration and temperature. The net (external K+-induced, depolarization-dependent) uptake follows a two-component course. The exponential term, due to the opening of voltage-operated calcium channels (VOC), has a rate constant which increases with an increase in the depolarization level (1.04 versus 0.54 nmol/s/mg protein for 50 mM - versus 15 mM (K+)-dependent net influx). The linear term, due to the Na{sup +}/Ca{sup 2+} exchange system, has a similar rate constant at all depolarization levels (0.16 +/- 0.05 and 0.11 +/- 0.02 nmol/s/mg protein). Excitatory amino acids (glutamate, kainate and n-methyl-d-aspartate-NMDA-) were tested on this preparation at doses ranging between 5 x 10(-5) M and 5 x 10(-3) M and at multiple incubation times, under resting conditions and under two depolarizing conditions (partial depolarization: 15 mM external K{sup +} and maximal depolarization: 50 mM external K+). NMDA was also tested in the absence of Mg{sup 2+}. No effect was detectable under any of these experimental conditions. Hypotheses to interpret these data are discussed. Further studies on other preparations are needed in order to directly investigate the presynaptic effects of excitatory amino acids.

  16. A phosphatidylinositol lipids system, lamellipodin, and Ena/VASP regulate dynamic morphology of multipolar migrating cells in the developing cerebral cortex.

    Science.gov (United States)

    Yoshinaga, Satoshi; Ohkubo, Takahiro; Sasaki, Shinji; Nuriya, Mutsuo; Ogawa, Yukino; Yasui, Masato; Tabata, Hidenori; Nakajima, Kazunori

    2012-08-22

    In the developing mammalian cerebral cortex, excitatory neurons are generated in the ventricular zone (VZ) and subventricular zone; these neurons migrate toward the pial surface. The neurons generated in the VZ assume a multipolar morphology and remain in a narrow region called the multipolar cell accumulation zone (MAZ) for ∼24 h, in which they extend and retract multiple processes dynamically. They eventually extend an axon tangentially and begin radial migration using a migratory mode called locomotion. Despite the potential biological importance of the process movement of multipolar cells, the molecular mechanisms remain to be elucidated. Here, we observed that the processes of mouse multipolar cells were actin rich and morphologically resembled the filopodia and lamellipodia in growth cones; thus, we focused on the actin-remodeling proteins Lamellipodin (Lpd) and Ena/vasodilator-stimulated phosphoprotein (VASP). Lpd binds to phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P₂] and recruits Ena/VASP, which promotes the assembly of actin filaments, to the plasma membranes. In situ hybridization and immunohistochemistry revealed that Lpd is expressed in multipolar cells in the MAZ. The functional silencing of either Lpd or Ena/VASP decreased the number of primary processes. Immunostaining and a Förster resonance energy transfer analysis revealed the subcellular localization of PI(3,4)P₂ at the tips of the processes. A knockdown experiment and treatment with an inhibitor for Src homology 2-containing inositol phosphatase-2, a 5-phosphatase that produces PI(3,4)P₂ from phosphatidylinositol (3,4,5)-triphosphate, decreased the number of primary processes. Our observations suggest that PI(3,4)P₂, Lpd, and Ena/VASP are involved in the process movement of multipolar migrating cells.

  17. The influences of reserpine and imipramine on the 5-HT2 receptor binding site and its coupled second messenger in rat cerebral cortex.

    Science.gov (United States)

    Lee, Ming-Jen; Wei, Jiann-Wu

    2013-08-31

    An investigation on the molecular mechanism of depression state, less attention was focused on changes at the intracellular messenger level. In this study the effects of reserpine, a monoamine depletor, and imipramine, an antidepressant, on serotonin-2 (5-HT2) receptor binding and its second messenger system of rat cerebral cortex were studied. The level of inositol 4-monophosphate (IP1) accumulation elicited by 100 microM 5-HT via activation of the 5-HT2 receptor on cerebral cortical slices at twelve hours after a single dose of reserpine (2 mg/kg, i.p.) was significantly higher in treated rats, when compared to that of saline-treated rats; this significant level lasted for at least four days. The level of IP1 accumulation in rat cerebral cortical slices elicited by 100 microM serotonin was higher in the group pretreated with reserpine (0.25 mg/kg/day) sub-chronically for seven days than the group pretreated with normal saline. In the receptor binding study, the maximum binding (B(max)) of 5-HT2 receptor binding was increased, when compared to the corresponding controls; whereas, the dissociation equilibrium constant (K(d)) value of the 5-HT2 receptor was found unchanged in the reserpine treated group. Increases in the sensitivity of phosphoinositol (PI) turnover coupled with the 5-HT2 receptor were also found in the long-term (21 days) low dose (0.1 mg/kg/day) administration of reserpine. However, a long-term administration of imipramine (10 mg/kg/day) reduced the function of the PI turnover coupled with the 5-HT2 receptor. Results obtained from the combined use of reserpine and imipramine demonstrated that this combination was able to antagonize the super-sensitivity of the second messenger responses in 5-HT2 receptor induced by long-term treatment with reserpine. Long-term treatment with reserpine but not imipramine also caused an increase in the B(max) of the 5-HT2 receptor. This up-regulation of the 5-HT2 receptor by reserpine could be antagonized by

  18. 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.

  19. Computational analysis of cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Hidemasa; Abe, Osamu; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan)

    2010-08-15

    Magnetic resonance imaging (MRI) has been used in many in vivo anatomical studies of the brain. Computational neuroanatomy is an expanding field of research, and a number of automated, unbiased, objective techniques have been developed to characterize structural changes in the brain using structural MRI without the need for time-consuming manual measurements. Voxel-based morphometry is one of the most widely used automated techniques to examine patterns of brain changes. Cortical thickness analysis is also becoming increasingly used as a tool for the study of cortical anatomy. Both techniques can be relatively easily used with freely available software packages. MRI data quality is important in order for the processed data to be accurate. In this review, we describe MRI data acquisition and preprocessing for morphometric analysis of the brain and present a brief summary of voxel-based morphometry and cortical thickness analysis. (orig.)

  20. Knockdown of Myo-Inositol Transporter SMIT1 Normalizes Cholinergic and Glutamatergic Function in an Immortalized Cell Line Established from the Cerebral Cortex of a Trisomy 16 Fetal Mouse, an Animal Model of Human Trisomy 21 (Down Syndrome).

    Science.gov (United States)

    Cárdenas, Ana María; Fernández-Olivares, Paola; Díaz-Franulic, Ignacio; González-Jamett, Arlek M; Shimahara, Takeshi; Segura-Aguilar, Juan; Caviedes, Raúl; Caviedes, Pablo

    2017-07-10

    The Na(+)/myo-inositol cotransporter (SMIT1) is overexpressed in human Down syndrome (DS) and in trisomy 16 fetal mice (Ts16), an animal model of the human condition. SMIT1 overexpression determines increased levels of intracellular myo-inositol, a precursor of phophoinositide synthesis. SMIT1 is overexpressed in CTb cells, an immortalized cell line established from the cerebral cortex of a Ts16 mouse fetus. CTb cells exhibit impaired cytosolic Ca(2+) signals in response to glutamatergic and cholinergic stimuli (increased amplitude and delayed time-dependent kinetics in the decay post-stimulation), compared to our CNh cell line, derived from the cerebral cortex of a euploid animal. Considering the role of myo-inositol in intracellular signaling, we normalized SMIT1 expression in CTb cells using specific mRNA antisenses. Forty-eight hours post-transfection, SMIT1 levels in CTb cells reached values comparable to those of CNh cells. At this time, decay kinetics of Ca(2+) signals induced by either glutamate, nicotine, or muscarine were accelerated in transfected CTb cells, to values similar to those of CNh cells. The amplitude of glutamate-induced cytosolic Ca(2+) signals in CTb cells was also normalized. The results suggest that SMIT1 overexpression contributes to abnormal cholinergic and glutamatergic Ca(2+) signals in the trisomic condition, and knockdown of DS-related genes in our Ts16-derived cell line could constitute a relevant tool to study DS-related neuronal dysfunction.

  1. Single-dose and chronic corticosterone treatment alters c-Fos or FosB immunoreactivity in the rat cerebral cortex.

    Science.gov (United States)

    Szakács, Réka; Fazekas, Ildikó; Mihály, András; Krisztin-Péva, Beáta; Juhász, Anna; Janka, Zoltán

    2010-03-01

    The aim of this study was to examine the effects of single-dose and chronic corticosterone treatment on the inducible transcription factor c-Fos and FosB, and thereby to estimate the effects of high-doses of corticosterone on calcium-dependent neuronal responses in the rat cerebral cortex. At the same time we investigated the distribution of interneurons containing calretinin (CR), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in chronically treated animals in order to collect data on the involvement of inhibitory neurons in this process. Adult male rats were injected subcutaneously with 10mg corticosterone, whereas controls received the vehicle (sesame oil). The animals were fixed by transcardial perfusion 12 and 24h following single corticosterone injection, and the brains were processed for c-Fos and FosB immunohistochemistry. To investigate the effects of repeated corticosterone administration, rats were daily treated with the same amount of corticosterone (10mg/animal, subcutaneously) for 21 days. Controls were injected with vehicle. At the end of the experiment, the rats were perfused and immunohistochemistry was used to detect the presence of the FosB protein, CR, VIP and NPY. Quantitative evaluation of immunolabelled cells was performed in the neocortex and the hippocampus. The number of immunoreactive nuclei per unit area was used as a quantitative measure of the effects of corticosterone. It was found that a single-dose administration of corticosterone resulted in a significant, time-dependent increase of c-Fos protein immunoreactivity in the granule cell layer of the dentate gyrus, as well as in regions CA1 and CA3 of the hippocampus 12 and 24h post-injection with respect to control animals. Significant enhancement of c-Fos immunoreactivity was also observed in the neocortex at 12 and 24h post-injection. Single-dose treatment did not significantly alter FosB immunolabelling. Repeated administration of corticosterone produced a complex

  2. 液质联用蛋白组学技术分析脑组织脂筏样品的属性*%Properties of Lipid Rafts from Cerebral Cortex Based on HPLC MS/MS Proteomics

    Institute of Scientific and Technical Information of China (English)

    聂坤; 张雪竹; 赵岚; 贾玉洁; 韩景献

    2013-01-01

      目的验证蔗糖密度梯度超速离心法提取脑组织脂筏的有效性。方法用蔗糖密度梯度超速离心法提取小鼠脑组织脂筏,采用免疫印迹法、双酶胆固醇检测法结合光散射度分析样品的脂筏属性,采用液质联用蛋白组学技术和生物信息学手段,对脂筏中的蛋白质细胞定位进行分析。结果超速离心法提取的脑组织脂筏具有典型的高散色度、高胆固醇和高表达Flotillin-1的脂筏特性;液质联用蛋白组学分析从脂筏样本中鉴定出647种蛋白质,这些蛋白质细胞定位大多是细胞膜、内质网、细胞骨架和细胞浆等常见的脂筏蛋白来源,这种脂筏样品是含有杂质的混合物,鉴定出的647种总蛋白中,有21%是细胞核、线粒体和核糖体等非脂筏来源蛋白。结论超速离心法是提取脑组织脂筏的有效方法,但应用中要考虑杂蛋白的影响。%Objective To verify the validity of the sucrose density gradient ultracentrifugation method for lipid rafts from cerebral cortex. Methods Extract lipid rafts from cerebral cortex in mouse were extracted by the sucrose density gradi-ent ultracentrifugation method. The properties of lipid rafts were detected by Western blotting method, double enzyme and light scattering methods. HPLC MS/MS proteomics and bioinformatics were used to locate proteins of lipid rafts in cells. Re-sults Lipid rafts from cerebral cortex were provided with the model properties of lipid rafts such as high light scattering and cholesterol and high expression of Flotillin-1. HPLC MS/MS proteomics identified total 647 proteins. Most of these pro-teins were from plasma membrane, endoplasmic reticulum, cytoskeleton and cytosol, however, there were 21% proteins among total 647 proteins were from nucleus, mitochondria and ribosomes. Conclusion The sucrose density gradient ultra-centrifugation method is a effective method to extract lipid rafts from cerebral cortex, however

  3. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces expression of p27(kip¹) and FoxO3a in female rat cerebral cortex and PC12 cells.

    Science.gov (United States)

    Xu, Guangfei; Liu, Jiao; Yoshimoto, Katsuhiko; Chen, Gang; Iwata, Takeo; Mizusawa, Noriko; Duan, Zhiqing; Wan, Chunhua; Jiang, Junkang

    2014-05-02

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent toxin that alters normal brain development, producing cognitive disability and motor dysfunction. Previous studies in rats have proved that female rats are more sensitive to TCDD lethality than male ones. Recent studies have shown that TCDD induces cell cycle arrest and apoptosis, but the regulatory proteins involved in these processes have yet to be elucidated. In this study, we constructed an acute TCDD injury female rat model, and investigated the effects of TCDD on apoptosis and expression of cell cycle regulators, forkhead box class O 3a (FoxO3a) and p27(kip1), in the central nervous system (CNS). Increased levels of active caspase-3 were observed in the cerebral cortex of female rats treated with TCDD, suggesting that TCDD-induced apoptosis occurs in the CNS. The terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling assay showed that apoptosis primarily occurred in neurons. Furthermore, Western blot analysis, reverse transcription-polymerase chain reaction, and immunohistochemistry showed a significant up-regulation of FoxO3a and p27(kip1) in the cerebral cortex. Immunofluorescent labeling indicated that FoxO3a and p27(kip1) were predominantly localized in apoptotic neurons, but not in astrocytes. In vitro experiments using PC12, a rat neuron-like pheochromocytoma cell line, also revealed that TCDD induced apoptosis and an increase in FoxO3a and p27(kip1) expression. Furthermore, knockdown of FoxO3a expression inhibited p27(kip1) transcription and TCDD-induced apoptosis. Based on our data, induction of FoxO3a may play an important role in TCDD-induced neurotoxicity.

  4. Screening and Identification of Natural Antisense Transcript in Mouse Cerebral Cortex%小鼠大脑皮层层次特异表达基因天然反义转录物的筛选与鉴定

    Institute of Scientific and Technical Information of China (English)

    李萍; 张靖; 李爱花; 王珊; 谈小超; 阴彬; 彭小忠

    2011-01-01

    目的 筛选并鉴定小鼠大脑皮层发育过程中皮层层次特异表达的基因是否存在天然反义转录物(NAT).方法 对63个小鼠大脑皮层层次特异表达的基因进行生物信息学预测,筛选出31个可能存在NAT的基因,从小鼠脑组织及神经系统来源的细胞系提取总RNA,采用RT-PCR方法对筛选阳性基因进行鉴定并克隆到pGEM-T载体中进行测序.结果 31个经生物信息学预测的基因中,8个为NAT阳性.结论 小鼠大脑皮层发育过程中皮层层次特异表达的基因存在NAT,NAT可能通过调控编码基因影响小鼠皮层发育.%Objective To screen and identify the possible existence of natural antisense transcript ( NAT) within the mouse neocortex. Methods Sixty-three cerebral cortex layer-specific genes were screened by bioinformatics prediction in mice, among which 31 mice with potential N Ats were screened. NAT was identified using reverse transcription polymerase chain reaction ( RT-PCR) and then cloned in pGEM-T Vector System for sequencing. Results Among 31 genes predicted using bioinformatics, 8 were proved to be NAT positive by RT-PCR. Conclusions NATs exist in the mouse neocortex tissue during the development of cerebral cortex. NATs may influence mouse cortical development by regulating the related coding genes.

  5. Changes of MCT2 expression in cerebral cortex after formalin-induced rat pain model%MCT2在福尔马林致痛模型大鼠大脑皮质中的表达变化

    Institute of Scientific and Technical Information of China (English)

    宋开琴; 康承巧; 孙善全; 黄娟; 徐进; 李文娟; 蒋锦

    2014-01-01

    目的:观察疼痛应激时,大脑第一躯体感觉皮质后肢区(primary somatosensory cortex hindlimb region,S1HL)神经元单羧酸转运蛋2(monocarboxylate transporters 2,MCT2)的表达变化,以探讨MCT2参与疼痛调制的机制。方法应用免疫组织化学(IHC)、Western blot和计算机图像分析法检测福尔马林致痛大鼠模型大脑S1HL内MCT2的表达变化。结果与正常组相比,模型鼠S1HL内MCT2阳性神经元的数量及IOD在1 h时增加,3 d时达高峰,到7 d时有所下降,但仍然高于正常水平(P<0.05)。Western blot结果显示,MCT2蛋白表达变化与MCT2阳性神经元的数量和IOD变化趋势一致。结论在疼痛应激状态下,大脑S1HL神经元MCT2的表达增强,提示MCT2参与了疼痛的产生、传递和调制过程。%Objective To investigate the changeofmonocarboxylate transporters 2( MCT2) expression in cerebral cortex primary somatosensory cortex hindlimb region(S1HL)under the condition of pain stimulation, so as to explore the involvement of MCT2 in the pain adjustment mechanism in a rat pain model. Methods Immunohistochemical staining(IHC), Western blot and Computing- image analysis system were used to detect the changes of MCT2 expression in the cerebral cortex S1HL of the formalin-induced rat pain model. Results Compared with the control group, the number and IOD of MCT2-positive neurons in the cerebral cortex S1HL of formalin-treated rats began to increase at 1h,reaching the highest level on 3d and declined on 7d ,but still higher than those in the control group (P<0.05).The Western blot showed that the alteration tendency of MCT2 expression was consistent with those of the number and IOD of MCT2-positive neurons. Conclusion Our results indicated that MCT2 is up-regulated under the condition of pain stimulation, which might be involved in the formalin-induced pain and behavior regulation.

  6. On the Parallel Between Zipf's Law and 1/f Processes\\in Chaotic Systems Possessing Coexisting Attractors --A Possible Mechanism for language Formation in the Cerebral Cortex--

    Science.gov (United States)

    Nicolis, J. S.; Tsuda, I.

    1989-08-01

    A chaotic dynamics model of creating Markovian strings of symbols as well as sequences of "words" is exposed, and its relevance to Zipf's law in experimental linguistics is discussed. Recent developments of brain science and linguistics suggest a preliminary theory of language formation by means of chaotic dynamics both in groups of cerebral neurons and the thalamocortical pacemaker itself.

  7. Changes of TNF-α in the Cortex of Rat Brain after Pure Cerebral Concussion%TNF-α在单纯性脑震荡大鼠皮质中的表达变化

    Institute of Scientific and Technical Information of China (English)

    李玉环; 吴德野; 董世峰; 唐红丹; 杨晓燕; 左寒东; 于建云; 李坪

    2015-01-01

    目的 观察单纯性脑震荡(pure cerebral concussion,PCC)大鼠前额叶皮质(prefrontal cortex,PC)、颞叶皮质(temporal cortex,TC)和梨状皮质(piriform cortex,Pir)区炎症因子TNF-α(tumor necrosis factor-α,TNF-α)的表达和时程变化规律,探讨TNF-α与脑损伤之间的病理联系.方法 采用“金属单摆闭合式脑损伤打击装置”制备PCC模型,随机分为伤后3h、12h、1d、2d、3d、7d6个时间点的PCC损伤组(n=5),另设正常对照组(n=5).采用兔抗TNF-α进行免疫组织化学SP法染色,观察PCC组和正常对照组大鼠PC、TC和Pir脑区TNF-α的表达变化.结果 正常对照组大鼠PC、TC和Pir内TNF-α免疫阳性表达很弱,损伤后TNF-α的阳性表达和阳性细胞的数量逐渐增加,3d组达高峰,7d组后有下降趋势,但仍高于正常组(P<0.05).结论 PCC损伤早期PC、TC和Pir中TNF-α的表达量出现明显变化,提示TNF-α参与了PCC致伤后的病理变化.

  8. Effects of nanometer particles and water decoction of the Chinese medicine mixture of pinellia ternate and scorpion on P53 protein contents and apoptosis in the cerebral cortex and hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Shuxiang Wang; Lei Liu; Yuming Kang; Shuqiu Wang; Dixiang Sun; Xiaoru Ma; Yanfeng Liang; Fangfang Wang

    2008-01-01

    BACKGROUND:Water decoction of the Chinese traditional mcdicine mixture of pinellia ternate and scorpion is an effective treatment for epilepsy.OBJECTIVE:To compare nanometer particles and effects of water decoction of Chinese traditional medicine mixture on P53 protein levels and apoptosis in the cerebral cortex and hippocampus of epileptic rats.DESIGN,TIME AND SETTING:This randomized,controlled molecular biology study was performed at the Key Laboratory of Child Neural Rehabilitation of Jiamusi University from October to December 2007.MATERIALS:Forty healthy male Wistar rats were used in this study.Convulsion rat models were established by intraperitoneal infusion of 35 mg/kg pentylenetetrazol,once a day,for 28 successive days.The Chinese traditional medicine mixture,comprising pinellia ternate,scorpion,centipede,bupleurum,peach pit and glycyrrhiza,was purchased from Beijing Tongrentang,China.The mixture was made into nanometer particles and water decoction.The apoptosis determination kit and P53 immunohistochemistry kit were bought from Boster,China.METHODS:Forty Wistar rats were randomlv divided into four groups of ten rats per group,control,nanometer particle,water decoction and epileptic model groups.Rats in the nanometer particle and water decoction groups were respectively treated with 300 mg/kg Chinese herb nanometer particle suspension and water decoction by gavage,once a day,for 28 days.Rats in the epileptic model group were fed an equal volume of saline by gavage.Rats in the control group were only administered with the same volume of saline by gavage.MAIN OUTCOME MEASURES:Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL)and immunohistochemistry were used to respectively detect neuronal apoptosis and P53 protein expression in the rat brain cortex and hippocampus at 28 davs following administration.RESULTS:The number of apoptotic neurons was lower in the nanometer particle and water decoction groups compared with the epileptic

  9. The coupling of cerebral blood flow and oxygen metabolism with brain activation is similar for simple and complex stimuli in human primary visual cortex.

    Science.gov (United States)

    Griffeth, Valerie E M; Simon, Aaron B; Buxton, Richard B

    2015-01-01

    Quantitative functional MRI (fMRI) experiments to measure blood flow and oxygen metabolism coupling in the brain typically rely on simple repetitive stimuli. Here we compared such stimuli with a more naturalistic stimulus. Previous work on the primary visual cortex showed that direct attentional modulation evokes a blood flow (CBF) response with a relatively large oxygen metabolism (CMRO2) response in comparison to an unattended stimulus, which evokes a much smaller metabolic response relative to the flow response. We hypothesized that a similar effect would be associated with a more engaging stimulus, and tested this by measuring the primary human visual cortex response to two contrast levels of a radial flickering checkerboard in comparison to the response to free viewing of brief movie clips. We did not find a significant difference in the blood flow-metabolism coupling (n=%ΔCBF/%ΔCMRO2) between the movie stimulus and the flickering checkerboards employing two different analysis methods: a standard analysis using the Davis model and a new analysis using a heuristic model dependent only on measured quantities. This finding suggests that in the primary visual cortex a naturalistic stimulus (in comparison to a simple repetitive stimulus) is either not sufficient to provoke a change in flow-metabolism coupling by attentional modulation as hypothesized, that the experimental design disrupted the cognitive processes underlying the response to a more natural stimulus, or that the technique used is not sensitive enough to detect a small difference. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Expression of Zonula Occludens-1 in Cerebral Cortex Following Traumatic Brain Injury%闭锁小带蛋白-1在脑外伤后皮质中的表达变化

    Institute of Scientific and Technical Information of China (English)

    王涛; 孟颖; 邹冬华; 李正东; 陈忆九; 陶陆阳

    2015-01-01

    目的:观察闭锁小带蛋白-1(zonula occludens-1,ZO-1)在脑外伤后皮质中不同时段的表达变化。方法建立小鼠脑外伤模型,分为脑外伤后1h、3h、6h、12h、24h、3d、7d组,同时设立假手术组及正常对照组。脑皮质中伊文思蓝(Evans blue,EB)含量检测评估血脑屏障通透性,Western印迹法和免疫组织化学染色法检测损伤皮质区ZO-1的表达。结果脑外伤后1 h皮质中EB含量开始增加,伤后1~3 d达高峰,伤后7 d接近正常。 Western印迹法显示,ZO-1在损伤1 h后表达下调,损伤1~3 d达到最低值,损伤7 d后明显回升,但仍低于假手术组和正常对照组。免疫组织化学染色显示,正常脑皮质血管中ZO-1呈强阳性表达,损伤后表达逐渐减弱,损伤3 d后阳性表达几乎消失,之后逐渐恢复。结论 ZO-1在脑外伤后皮质区呈先降低后升高的表达规律,与脑外伤后血脑屏障通透性变化规律呈负相关,为推断脑外伤损伤时间提供了新指标。%Objective To observe the time-course expression of zonula occludens-1 (ZO-1) in cerebral cortex after traumatic brain injury (TBI). Methods The TBI model of mouse was established. The mice were divided in 1 h, 3 h, 6 h, 12 h, 24 h, 3 d, 7 d after TBI, shamand control groups. The permeability of the blood brain barrier was evaluated by measuring the extravasation of Evans blue (EB) dye. The expression of Z O-1 in cerebral cortex in the injured area was detected by western blotting and im-munohistochemistry. Results The extravasation of EBdye of injured cortex gradually increased from 1 h, peaked at 1-3 d and approximately decreased to normal at 7 d after TBI. western blotting revealed that the expression of Z O-1 gradually decreased after 1 h, was at the lowest at 1-3 d, and then significantly increased after 7 d but was still lower than that of normal and shamgroups. The result of immunohisto-chemistry showed that Z O-1 had strong

  11. Clinical Neuroimaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji [Nakamura Memorial Hospital, Sapporo (Japan)

    1999-06-01

    Notice points in clinical imaging of cerebral ischemia are reviewed. When cerebral blood flow is determined in acute stage of cerebral embolism (cerebral blood flow SPECT), it is important to find area of ischemic core and ischemic penumbra. When large cortex area is assigned to ischemic penumbra, thrombolytic therapy is positively adapted, but cautious correspondence is necessary when ischemic core is recognized. DWI is superior in the detection of area equivalent to ischemic core of early stage, but, in imaging of area equivalent to ischemic penumbra, perfusion image or distribution image of cerebral blood volume (CBV) by MRI need to be combined. Luxury perfusion detected by cerebral blood flow SPECT in the cases of acute cerebral embolism suggests vascular recanalization, but a comparison with CT/MRI and continuous assessment of cerebral circulation dynamics were necessary in order to predict brain tissue disease (metabolic abnormality). In hemodynamic cerebral ischemia, it is important to find stage 2 equivalent to misery perfusion by quantification of cerebral blood flow SPECT. Degree of diaschisis can indicate seriousness of brain dysfunction for lacuna infarct. Because cerebral circulation reserve ability (perfusion pressure) is normal in all areas of the low cerebral blood flow by diaschisis mechanism, their areas are easily distinguished from those of hemodynamic cerebral ischemia. (K.H.)

  12. Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

    Directory of Open Access Journals (Sweden)

    Quartu Marina

    2012-01-01

    Full Text Available Abstract Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O., a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R. 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA, the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2, as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA, and levels of palmytoylethanolamide (PEA and oleoylethanolamide (OEA. Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR alpha activation, protecting brain tissue from ischemia/reperfusion injury.

  13. Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

    Directory of Open Access Journals (Sweden)

    Donatella Marazziti

    2007-06-01

    Full Text Available OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4 no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745

  14. 慢性间断性低氧大鼠脑皮层GAP-43表达的时间变化%Time variation of the growth associated protein expression on the cerebral cortex in chronic intermittent hypoxia rats

    Institute of Scientific and Technical Information of China (English)

    陈燕; 赵春玲; 罗礼容; 余广; 张春来

    2013-01-01

    Objective To observe the time variation of the growth associated protein on the cerebral cortex in chronic intermittent hypoxia rats for discussing the relation between the change and neural repair after hypoxic brain damage.Methods Forty adult male Sprague-Dawley rats were randomly averagely divided into four groups:control group,CIH 1 week group,CIH 3 weeks group and CIH 5 weeks group.CIH-handled rats were exposed to intermittent hypoxia in designed cabin 8 hours every day,and the duration of hypoxia was 1 weeks,3 weeks,5 weeks.The GAP-43 expression of hippocampus were detected by immunohistochemical staining.Results Compared with the control group,the GAP-43expression in cerebral cortex was increased in CIH rats.The peak of GAP-43 expression appeared at 1 week(P<0.05)and then it reduced at 3 weeks(P<0.05)and it was closed to the level of control group at 5 weeks(P>0.05).Conclusion There was the time variation of the growth associated protein expression on the cerebral cortex in chronic intermittent hypoxia rats,which maybe associated with the compensatory repair to against chronic intermittent hypoxia.%目的 观察慢性间断性低氧(CIH)大鼠脑皮层生长相关蛋白(GAP-43)表达的时间变化,探讨这些变化与缺氧性脑损伤修复间的关系.方法 成年雄性SD大鼠40只,随机均分为对照组、CIH 1周、CIH 3周和CIH 5周组.CIH组大鼠在自制缺氧舱内每天缺氧8小时,连续缺氧1、3和5周.利用免疫组化方法检测大脑皮层神经元生长相关蛋白的表达.结果 与对照组比较,慢性间断性低氧大鼠脑皮层神经元GAP-43阳性表达增多,表达高峰出现在1周后(P<0.05),3周后表达逐渐减少(P>0.05),5周后表达接近对照组水平(P>0.05).结论 慢性间断性低氧大鼠脑皮层生长相关蛋白的表达呈现时间变化,这可能与缺氧性脑损伤后的修复有关.

  15. FGF-2 deficiency causes dysregulation of Arhgef6 and downstream targets in the cerebral cortex accompanied by altered neurite outgrowth and dendritic spine morphology.

    Science.gov (United States)

    Baum, Philip; Vogt, Miriam A; Gass, Peter; Unsicker, Klaus; von Bohlen und Halbach, Oliver

    2016-05-01

    Fibroblast growth factor 2 (FGF-2) is an abundant growth factor in the brain and exerts multiple functions on neural cells ranging from cell division, cell fate determination to differentiation. However, many details of the molecular mechanisms underlying the diverse functions of FGF-2 are poorly understood. In a comparative microarray analysis of motor sensory cortex (MSC) tissue of adult knockout (FGF-2(-/-)) and control (FGF-2(+/+)) mice, we found a substantial number of regulated genes, which are implicated in cytoskeletal machinery dynamics. Specifically, we found a prominent downregulation of Arhgef6. Arhgef6 mRNA was significantly reduced in the FGF-2(-/-) cortex, and Arhgef6 protein virtually absent, while RhoA protein levels were massively increased and Cdc42 protein levels were reduced. Since Arhgef6 is localized to dendritic spines, we next analyzed dendritic spines of adult FGF2(-/-) and control mouse cortices. Spine densities were significantly increased, whereas mean length of spines on dendrites of layer V of MSC neurons in adult FGF-2(-/-) mice was significantly decreased as compared to respective controls. Furthermore, neurite length in dissociated cortical cultures from E18 FGF-2(-/-) mice was significantly reduced at DIV7 as compared to wildtype neurons. Despite the fact that altered neuronal morphology and alterations in dendritic spines were observed, FGF-2(-/-) mice behave relatively unsuspicious in several behavioral tasks. However, FGF-2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test.

  16. 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

  17. HISTOCHEMICAL STUDY OF THE AFFECTION OF TEMPORARY CEREBRAL ISCHEMIA ON THE CEREBELLAR CORTEX%短暂性缺血对小脑皮质影响的组织化学研究

    Institute of Scientific and Technical Information of China (English)

    李仁; 顾远清; 陈显斌; 李昊; 熊希凯; 吴刚

    2001-01-01

    In order to explore the affection of temporary cerebral ischemiaon the purkinje cells of the cerebellary cortex. Using histochemical method, enzymehistochemical changes was observed in the purkinje cells of the rabbit after ischemia of 5 minutes (group B)、 10 minutes (group C) and reperfusion (group D、E). The results showed that after 10 minutes of ischemia and reperfusion. The activites of SDH、Mg2+-ATP、PAS were reduced (P<0.05), While the activites of LDH wre increased (P<0.01). The results suggested that the injury of 10 minutes ischemia and reperfusion may damage the activites of enzymes associated with energic metabolism in cerebellar cortex of purkinje cells.%为了探讨全脑短暂性缺血对小脑皮质蒲肯野细胞的影响,实验用组织化学方法对家兔全脑缺血5分钟(B组)、10分钟(C组)及缺血再灌(D、E组)后蒲肯野细胞的酶组织化学变化进行了观察。结果显示,缺血10分钟及缺血再灌后蒲肯野细胞的SDH、Mg2+-ATP活性及PAS反应均降低(P<0.05),LDH增高(P<0.01)。结果提示家兔全脑缺血10分钟和缺血再灌可损害小脑皮质蒲肯野细胞的能量代谢酶的活性。

  18. Effect of epileptogenic agents on the incorporation of /sup 3/H-glycine into proteins in the cat's cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Rojik, I.; Feher, O.

    1982-06-01

    Filter paper strips soaked in /sup 3/H-glycine solution were applied to acoustic cortex of cats, anaesthetized with Nembutal and pretreated with epileptogenic agents (Metrazol, G-penicillin, and 3-amino-pyridine) and cycloheximide. The untreated contralateral hemisphere served as control. After 1 h incubation, both cortical samples were excised simultaneously and fixed in Bouin solution for autoradiography. Incorporation was blocked by cycloheximide. There was no glycine incorporation on the penicillin-treated side, while pyramidal cells were intensively labelled in layers II-V of the mirror focus. 3-Aminopyridine produced the same result. Metrazol as convulsant proved to be far weaker than the previous two. The intensity of incorporation was significantly more intensive in the mirror focus than in the primary one. Penicillin and 3-aminopyridine, while provoking cortical seizures, seem to inhibit glycine incorporation into a neuron-specific, function-dependent protein contained by the labelled cells in the autoradiogram.

  19. Structural asymmetry of the human cerebral cortex: Regional and between-subject variability of surface area, cortical thickness, and local gyrification.

    Science.gov (United States)

    Chiarello, Christine; Vazquez, David; Felton, Adam; McDowell, Alessandra

    2016-12-01

    Structural asymmetry varies across individuals, brain regions, and metrics of cortical organization. The current study investigated regional differences in asymmetry of cortical surface area, thickness, and local gyrification, and the extent of between-subject variability in these metrics, in a sample of healthy young adults (N=200). Between-subject variability in cortical structure may provide a means to assess the extent of biological flexibility or constraint of brain regions, and we explored the potential influence of this variability on the phenotypic expression of structural asymmetry. The findings demonstrate that structural asymmetries are nearly ubiquitous across the cortex, with differing regional organization for the three cortical metrics. This implies that there are multiple, only partially overlapping, maps of structural asymmetry. The results further indicate that the degree of asymmetry of a brain region can be predicted by the extent of the region's between-subject variability. These findings provide evidence that reduced biological constraint promotes the expression of strong structural asymmetry.

  20. Label-free in vivo optical micro-angiography imaging of cerebral capillary blood flow within meninges and cortex in mice with the skull left intact

    Science.gov (United States)

    Jia, Yali; Wang, Ruikang K.

    2011-03-01

    Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of visualizing functional meningeal microcirculations alone, preferably decoupled from the cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to the blood flow at ~4 μm/s. In this study, we demonstrate the utility of ultra-high sensitive OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within meninges and cortex in mice with the cranium left intact. The results indicate that OMAG can be a valuable tool for the study of meningeal circulations.

  1. 脑缺血后大脑皮质神经生长因子和脑源性神经营养因子的改变%The Change of Nerve Growth Factor and Brain Derived Neurotrophic Factor in Neurons of Cerebral Cortex of Adult Rat Following Local Ischemia

    Institute of Scientific and Technical Information of China (English)

    曾兢; 王廷华; 张晓; 米兰兰; 高礼

    2001-01-01

    【内容摘要】目的探讨脑缺血后大脑皮质神经生长因子(NGF)、脑源性神经营养因子(BDNF)的变化。方法采用免疫组织化学ABC法观察NGF和BDNF的改变。结果 NGF、BDNF样免疫阳性反应物主要分布于大脑皮质第3、5层的神经元。脑缺血1小时后,NGF、BDNF在皮质神经元的表达明显增加。结论 NGF、BDNF与脑缺血后大脑皮质神经细胞的损伤修复有关。%Objective To acquire knowledge about the change of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in neurons of cerebral cortex of adult rat following local ischemia. Methods Using specific antiserums of NGF and BDNF by immunohistochemical ABC method. Results NGF-like and BDNF-like immunoreactions distributed mainly in the neurons of the third and fifth layers in cerebral cortex. After local ischemia, the average gray degrees of NGF and BDNF in neurons of cerebral cortex both decreased on the operated side more than on the un-operated side. Conclusion This experiment demonstrated that the levels of NGF and BDNF in neurons of cerebral cortex following ischemia were upregulated apparently, suggesting that NGF and BDNF may play an important role in the process of neurons' reaction after ischemia.

  2. The expression of cholecystokinin and prolactin in cerebral cortex of developing rats with seizure induced by acute heat stress%发育期热水浴诱发惊厥大鼠大脑皮层催乳素和胆囊收缩素蛋白表达的研究

    Institute of Scientific and Technical Information of China (English)

    陈大庆; 倪宏; 水泉祥; 丁振尧; 李上淼

    2009-01-01

    Objective To analyze the distribution of cholecystokinin (CCK) and prolactin (PRL) positive cells in rat' s brain following heat stress (HS) and febrile convulsion ( FC). Methods Acute heat stress model of seizure induced by warm water was developed in this study. Adjacent section immunohistochemical staining method was used to observe expression of CCK and PRL in cerebral cortex. Results (1) There were similar distributions of CCK and PRL positive cells in cerebral cortex of HS group. (2) Both HS and FC rats showed more positive neurons in cerebral cortex than those in control group (P < 0. 01). There were significant more CCK positive neurons in cerebral cortex than that in HS group(P <0. 01) .however,no significant difference of PRL positive neurons was found in piriform cortex and entorhinal cortex between HS and FC group(P>0.05) ,but the difference was significant in perirhinal cortex and parietal cortex. (3)Correlation and regression analysis of the data of CCK and PRL positive units demonstrated that the immunoreactive intensity of CCK and PRL had a positive linear correlation in cerebral cortex of HS group ( Y = 7. 939 +1. 36X, r = 0. 97, P < 0. 01), but no correlation was found in cerebral cortex of FC group ( r = 0. 47, P >0.05). Conclusion (1) CCK may involve in anti-convulsant mechanisms in response to FC. (2) There may be a synergistic action of PRL and CCK in the central control of HS.%目的 探讨急性热应激(HS)和热性惊厥(FC)对大脑皮层胆囊收缩素(CCK)和催乳素(PRL)定位表达的影响.方法 采用热水浴诱导21 日龄大鼠FC模型,应用免疫组织化学技术,对HS和FC大鼠CCK和PRL在大脑皮层的定位表达进行比较分析.结果 (1)HS组CCK和PRL阳性细胞在大脑皮层分布极为相似,免疫染色有共深或共浅的倾向.(2)HS组和FC组大脑皮层CCK、PRL阳性细胞数明显高于对照组(P<0.01).FC组大鼠大脑皮层各区CCK阳性细胞数明显高于HS组(P<0.01).FC组大鼠大

  3. Repeated low-dose 17β-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia.

    Science.gov (United States)

    Stanojlović, Miloš; Zlatković, Jelena; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zarić, Marina; Horvat, Anica; Drakulić, Dunja

    2015-01-01

    Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17β-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 µg/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Bax and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes.

  4. 小胶质细胞在单纯性脑震荡大鼠皮质中的变化%Changes of microglia in the cortex of rat brain after pure cerebral concussion

    Institute of Scientific and Technical Information of China (English)

    李晓文; 曾晓锋; 康丽; 吴德野; 郭小兵; 于建云; 李坪

    2014-01-01

    目的:观察单纯性脑震荡(pure cerebral concussion,PCC)大鼠前额叶皮质(prefrontal cortex,PC)、颞叶皮质(temporal cortex,TC)和梨状皮质(piriform cortex,Pir)内小胶质细胞(microglia,MG)的反应和时程变化规律,探讨小胶质细胞与脑损伤之间的病理联系.方法:采用自制金属单摆闭合式脑损伤打击装置制备清醒状态下PCC模型,随机分为伤后3h、12 h、1d、2d、3d、7d六个损伤组(n=5),另设正常对照组(n=5).采用OX-42单克隆抗体(MG特异性标记物)进行免疫组织化学和免疫荧光染色,观察PCC组和正常对照组大鼠PC、TC和Pir中OX-42的表达变化.结果:正常对照组大鼠PC、TC和Pir内OX-42免疫阳性产物的表达很弱,OX-42免疫阳性的小胶质细胞的数量少而轮廓不清.损伤后OX-42免疫阳性产物的表达和阳性细胞的数量逐渐增加,3d时达高峰,7d后有下降趋势,但仍高于正常组(P<0.05).结论:PCC损伤早期PC、TC和Pir中MG出现激活的形态学变化,提示MG可能参与了PCC致伤后的病理变化.

  5. Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants on. beta. -adrenoceptors and 5-HT/sub 2/ binding sites in the rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Hall, H.; Ross, S.B.; Saellemark, M. (Astra Pharmaceuticals AB, Soedertaelje (Sweden))

    1984-01-01

    The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number of ..beta..-adrenoceptors and 5-HT/sub 2/ binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined. Noradrenergic nerve terminals were destroyed with the selective noradrenaline neurotoxin DSP4, and serotonergic nerve terminals were destroyed with p-chloroamphetamine (PCA). It was found that lesioning of the noradrenergic nerve terminals abolished the decrease in ..beta..-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of the ..beta..-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on the ..beta..-adrenoceptor produced by these compounds. Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT/sub 2/ binding sites produced by long-term treatment with mianserin, desipramine and amiflamine. DSP4 pretreatment partially abolished the down-regulation of 5-HT/sub 2/ binding sites produced by long-term treatment with desipramine, while the effects of mianserin and amiflamine were inaffected by pretreatment with DSP4.

  6. Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice.

    Science.gov (United States)

    Molinaro, Gemma; Battaglia, Giuseppe; Riozzi, Barbara; Di Menna, Luisa; Rampello, Liborio; Bruno, Valeria; Nicoletti, Ferdinando

    2009-04-10

    A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K(+)/Cl(-) co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl(-) concentrations, which drive Cl(-) influx in response to GABA(A) receptor activation, we monitored the behavioural response to the GABA(A) receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABA(A) receptors that might contribute to the therapeutic and/or toxic effects of the drug.

  7. A change of the expression of PLP in the prefrontal cortex of brain after pure cerebral concussion and multiple cerebral concussions in rats%一重和多重脑震荡大鼠前额叶髓鞘脂蛋白(PLP)的变化

    Institute of Scientific and Technical Information of China (English)

    江东; 李坪; 朱乔; 于建云; 张桓; 曹珍珍; 郭泽云

    2012-01-01

    Objective; This study aimed to investigate the distribution and expression changes of the myelin protein lipo-protein ( PLP) in prefrontal-septum areas after pure cerebral concussion ( PCC) and multiple cerebral concussions ( MCC). Methods:PCC and MCC rat models were created by using a metallic pendulum-striker concussive device. The rats were randomly divided into PCC 1,2,4,8 and 16 d (n = 6 for each time point) and MCC 1,2,4,8 and 16 d ( n = 6 for each time point) groups after injury. One control (normal) group (n =6) was used. The distribution and immno-expression changes of the PLP were observed by S-P immuno-histochemical staining in the prefrontal-septum areas after injury. Results: The results showed that PLP immunoreactivity was localized in the white matter and was widely associated with the nerve fibers in the molecular and granular layer of cerebral cortex and prefrontal-septum areas including medial forebrain bundle (Mfb) , vertical diagonal band (VDB) , lateral septal nucleus, intermediate part (LSI) , amygdaloid nucleus, corpus callosum (cc) , caudate putamen (Cpu) and anterior commissure (ac) in the control rats. Following PCC, the expression level of PLP in most areas was remained unaltered (P > 0. 05 ) compared to that of the control groups. However, in MCC groups, PLP expression was reduced significantly (P<0.05) in the molecular layer of pre-frontal cortex, VDB as well as the Cpu when compared with the control and PCC rats. Conclusion:The present results suggest that MCC may have cumalative effects on the injury, thus aggravating the damage to the nerve fibers of the pre-frontal-septum.%目的:为探索一重(pure cerebral concussion,PCC)和多重脑震荡(multiple cerebral concussion,MCC)后大鼠前额叶中隔断面髓鞘脂蛋白(myelin protein lipoprotein,PLP)分布与表达变化规律.方法:采用自制单摆式机械打击装置复制PCC和MCC大鼠模型,伤后随机分为PCC中1、2、4、8、16和24 d组(n=6),MCC中1、2、4、8、16

  8. 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.

  9. Cultivation of Cerebral Cortex Neuronal Cells of Newborn BALB/c Mice%新生BALB/c小鼠大脑皮质神经元细胞培养方法的建立

    Institute of Scientific and Technical Information of China (English)

    辛岗; 苏芸; 王革非; 许燕璇; 李康生

    2011-01-01

    Objective: To establish a method for cultivation of cerebral cortex neuronal cells of newborn BALB/c mice. Methods: The cortexes from newborn(less than 24 h) BALB/c mice were obtained and digested by 0.25% trypsin, and then dissociated into single cell suspension. About 1×106 cells were seeded onto each 35 mm dish which was coated by poly-L-lysine overnight previously. After cultivated in seeding medium for 6 h, the neuron cells were cultured in neurobasal medium containing B27, FBS, and glutamine. Cytosine arabinofurannside was added to the cultures at a final concentration of 5 mg/mL on 40 h. Results: The neuron cells showed a typical morphorlogy at day 5. As indicated by indirect immunofluorescence using antibodies against neuron specific βⅢ tubulin, the purity of the neuronal cultures was 93%. Conlusion: The optimized method to culture neuron from BALB/c mice was established.%目的:经改良和优化,建立高纯度BALB/c小鼠大脑皮质神经元培养的方法.方法:采用L-多聚赖氨酸包被细胞培养板,取新生BALB/c小鼠(出生24 h内)大脑皮质组织,经0.25%胰酶消化后吹打成单个细胞,按1×106/孔接种于35 mm的六孔板中,用神经元细胞培养种植液培养6 h后换神经元细胞培养饲养液,培养40 h时加入阿糖胞苷抑制神经胶质细胞的生长,随时观察神经元培养情况.结果:培养5 d的神经元细胞形态最为典型;经免疫荧光方法鉴定,神经元细胞纯度为93%.结论:经方法改良与优化,获得了高纯度的原代培养小鼠大脑皮质神经元细胞.

  10. Alpha-actinin expression at different differentiating time points from temporal lobe cerebral cortex neural stem cells to neuron-like cells using energy dispersive X-ray analysis

    Institute of Scientific and Technical Information of China (English)

    Bo YU; Hua Li; Zhe Du; Yang Hong; Meng Sang; Yuxiu Shi

    2009-01-01

    BACKGROUND: Alpha-actinin (a-actinin) plays a key role in neuronal growth cone migration during directional differentiation from neural stem cells (NSCs) to neurons.OBJECTIVE: To detect in situ microdistribution and quantitative expression of a-actinin during directional differentiation of NSCs to neurons in the temporal lobe cerebral cortex of neonatal rats.DESIGN, TIME AND SETTING: Between January 2006 and December 2008, culture and directional differentiation of NSCs were performed at Department of Histology and Embryology, Preclinical Medical College, China Medical University. Immune electron microscopy was performed at Department of Histology and Embryology and Department of Electron Micrology, Preclinical Medical College, China Medical University. Spectrum analysis was performed at Laboratory of Electron Microscopy, Mental Research Institute, Chinese Academy of Sciences.MATERIALS: Basic fibroblast growth factor, epidermal growth factor, brain-derived nerve growth factor, type-1 insulin like growth factor, and a-actinin antibody were provided by Gibco BRL, USA; rabbit-anti-rat nestin monoclonal antibody, rabbit-anti-rat neuron specific enolase polyclonal antibody, and EDAX-9100 energy dispersive X-ray analysis were provided by PHILIPS Company, Netherlands.METHODS: NSCs, following primary and passage culture, were differentiated with serum culture medium (DMEM/F12+10% fetal bovine serum+2 ng/mL brain-derived nerve growth factor+2 ng/mL type-1 insulin like growth factor).MAIN OUTCOME MEASURES: Expression of a-actinin in neuron-like cells was quantitatively and qualitatively detected with immunocytochemistry using energy dispersive X-ray analysis. RESULTS: Immunocytochemistry, combined with electron microscopy, indicated that positive a-actinin expression was like a spheroid particle with high electron density. In addition, the expression was gradually concentrated from the nuclear edge to the cytoplasm and expanded into developing neurites, during

  11. 脑桥出血早期患者脑皮质结构变化的磁共振研究%Magnetic resonance imaging of structural change in the cerebral cortex for early pons hemorrhage patients

    Institute of Scientific and Technical Information of China (English)

    莫本成; 张自力; 敖锋; 刘振华; 杨凡; 李华菊

    2016-01-01

    目的:探讨脑桥出血早期患者脑皮质结构变化,并分析与感觉运动功能损伤的相关性。方法选择2014年5月至2015年3月本院接诊的16例脑桥出血患者进行研究将其作为观察组,选取同期16例健康者作为对照组。观察组患者入院后给予结构磁共振( MRI)检测,通过基于体素形态学方法对MRI的结构数据进行分析,比较两组患者大脑灰质体积区域的改变。并通过相关性分析患者脑皮质结构的改变与运动感觉功能的关系。结果两组患者在年龄与性别方面差异无统计学意义( P>0.05);观察组的轻触觉评分、针刺觉评分以及运动评分均低于对照组,两组比较差异具有统计学意义( P<0.001);基于体素形态学方法分析结果显示,观察组的双侧初级感觉中心、初级运动中心及其辅助运动区发生了灰质体积减小的现象( P<0.05);观察组结构异常区域萎缩发生程度经相关分析与轻触觉评分、针刺觉评分以及运动评分无相关性( P>0.05)。结论脑桥出血早期患者初级感觉中心、初级运动中心及其辅助运动区发生了灰质萎缩,但是萎缩程度与患者轻触觉评分、针刺觉评分以及运动评分无关。%Objective To evaluate the structural change in the cerebral cortex for early pons hemorrhage patientsandanalysissensorymotorfunctionimpairement.Methods 16patientswithpontinehemorrhagefromMay 2014 to March 2015 in our hospital were researched as observer group.Select the same period 16 cases of healthy people as a control group.After admission, observation group structure of magnetic resonance detection, analysis the method based voxel morphology structure of magnetic resonance data,compare two groups of patients with brain gray matter volume area change, And through the correlation analysis of structural changes in the patients with cerebral cortex and the relationship between the

  12. Dynamic changes of apoptosis in rat cerebral cortex neurons after hypoxia%大鼠大脑皮层神经元缺氧后细胞凋亡情况的动态观察

    Institute of Scientific and Technical Information of China (English)

    邹哲华; 陶陶; 徐坚; 刘智; 罗开俭

    2012-01-01

    Objective To observe the dynamic changes of apoptosis in rat cerebral cortex neurons after hypoxia. Methods Rat cerebral cortex neurons were primarily cultured from SD rats born within 24 h and then identified by immunocytochemical assay. Then the identified cells were cultured in the medium containing 100 μmol/L CoCl2 to simulate hypoxic condition. The cells cultivated in normal condition served as normal control ( normoxia group). Ultrastructural changes of the neurons were observed by transmission electron microscopy (TEM) . Neuronal apoptosis were observed by TUNEL assay. Results TEM displayed that the morphology of neurons was normal, so was the structure of chromatin, endoplasmic reticulum and mitochondria in normoxia group, while, cellular edema, organelle damage or disappearance were seen in the hypoxia group. TUNEL showed that obvious apoptosis were found in hypoxic cells, with significant difference with normoxia group ( P < 0. 01). The apoptosis reached its peak in 48 h after hypoxia (0. 187 ±0. 007) , significantly higher than those in 12, 24 and 72 h (P <0. 01). Conclusion Apoptosis is a dynamic process in hypoxic-ischemic brain injury, and an important pattern of neuronal death. Intervention for neuronal apoptosis should be performed in an appropriate time window to effectively treat hypoxic-ischemic encephalopathy.%目的 观察大鼠大脑皮层神经元缺氧后细胞凋亡动态变化.方法 制备大鼠大脑皮层神经元体外原代培养模型,免疫细胞化学鉴定大鼠大脑皮层神经元,透射电镜下观察不同时间点各实验组神经元超微结构的变化,TUNEL法观察不同时间点各实验组神经元凋亡情况.结果 正常对照组神经元透射电镜下形态及染色质正常、内质网、线粒体等结构正常,缺氧组神经元水肿,细胞器破坏或消失;TUNEL法检测神经元凋亡:缺氧后各组神经元凋亡明显增加,与相应正常对照组相比有显著差异(P<0.01),缺氧48 h

  13. The value of qualitative and quantitative assessment of lesion to cerebral cortex signal ratio on double inversion recovery sequence in the differentiation of demyelinating plaques from non-specific T2 hyperintensities

    Energy Technology Data Exchange (ETDEWEB)

    Hamcan, Salih; Battal, Bilal; Akgun, Veysel; Sari, Sebahattin; Tasar, Mustafa [Gulhane Military Medical School, Department of Radiology, Etlik, Ankara (Turkey); Oz, Oguzhan; Tasdemir, Serdar [Gulhane Military Medical School, Department of Neurology, Ankara (Turkey); Bozkurt, Yalcin [Golcuk Military Hospital, Department of Radiology, Kocaeli (Turkey)

    2017-02-15

    To assess the usefulness of the visual assessment and to determine diagnostic value of the lesion-to-cerebral cortex signal ratio (LCSR) measurement in the differentiation of demyelinating plaques and non-specific T2 hyperintensities on double inversion recovery (DIR) sequence. DIR and fluid-attenuated inversion recovery (FLAIR) sequences of 25 clinically diagnosed multiple sclerosis (MS) patients and 25 non-MS patients with non-specific T2-hyperintense lesions were evaluated visually and LCSRs were measured by two observers independently. On DIR sequence, the calculated mean LCSR ± SD for demyelinating plaques and non-specific T2-hyperintense lesions were 1.60 ± 0.26 and 0.75 ± 0.19 for observer1, and 1.61 ± 0.27 and 0.74 ± 0.19 for observer2. LCSRs of demyelinating plaques were significantly higher than other non-specific T2-hyperintense lesions on DIR sequence. By using the visual assessment demyelinating plaques were differentiated from non-specific T2-hyperintensities with 92.8 % sensitivity, 97.5 % specificity and 95.1 % accuracy for observer1 and 92.8 % sensitivity, 95 % specificity and 93.9 % accuracy for observer2. Visual assessment and LCSR measurement on DIR sequence seems to be useful for differentiating demyelinating MS plaques from supratentorial non-specific T2 hyperintensities. This feature can be used for diagnosis of MS particularly in patients with only supratentorial T2-hyperintense lesions who are categorized as radiologically possible MS. (orig.)

  14. Frontoparietal cortical atrophy with gliosis in the gray matter of cerebral cortex: case report Atrofia cortical frontoparietal com gliose na substância cinzenta do córtex cerebral: relato de caso

    Directory of Open Access Journals (Sweden)

    Paulo Roberto de Brito-Marques

    2002-06-01

    região periventricular, centro semi-oval bilateral, e alta hiperintensidade de sinal na região da cápsula interna esquerda, além de leve atrofia bilateral nos lobos frontoparietais. Tomografia cerebral por emissão de fóton único revelou hipoperfusão de intensidade moderada nos lobos frontais e severa nos parietais, especialmente à esquerda. Os achados de necrópsia evidenciaram atrofia cortical, sendo severa nos lobos frontais, moderada nos parietais e leve no terço posterior dos temporais. Havia também leve atrofia no neostriado. Do ponto de vista histopatológico, existia na camada cortical severa perda neuronal com intensa gliose gemioscítica e grau variável de status spongiosus. As colorações por hematoxilina-eosina e Bielschowsky não revelaram células baloniformes (células de Pick e corpúsculos argirofílicos (corpos de Pick, degeneração neurofibrilar ou placa senil. As reações imuno-histoquímicas foram negativas para anti-ubiquitina, anti-tau, anti-beta amilóide e proteína anti-prion.

  15. 急性脑梗死康复治疗对手运动中枢激活区BOLD-fMRI偏侧化的影响%Lateralization in the hand motor cortex during rehabilitation after acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    周福玲; 元小冬; 王守红

    2013-01-01

    Objective To observe any change in the laterality index (LI) in the active volume of the hand motor cortex during rehabilitation after acute cerebral infarction and to analyze the mechanisms involved in the rehabilitation of motor function.Methods Sixteen patients with acute cerebral infarcts were administered standard but individualized rehabilitation training.Blood oxygenation-dependent functional magnetic resonance imaging (BOLD-fMRI) was used to evaluate the active volume of their hand sensorimotor cortex (SMC) and the LI,at admission and after 14 days of rehabilitation.The Fugl-Meyer motor assessment for the hand (FMA) was used to evaluate hand function.Ten healthy volunteers were recruited as a control group and subjected to a single BOLD-fMRI examination to confirm the location and the volume of the active area when performing the same rehabilitation exercises.Results The baseline LI of affected hand SMC activation was significantly smaller than that of the unaffected hand [(0.010 ±0.808) versus (0.789 ± 0.157)],but no significant difference was observed between the affected and the unaffected hands after treatment.Rehabilitation therapy significantly increased the SMC LI of affected hand activation when compared with the baseline,but no such effect was observed with the unaffected hand.In 12 patients with dysfunction of the right hand as evaluated by the FMA,the baseline LI of the affected hand was smaller than that of the unaffected hand and that of the healthy volunteers.Conclusion Rehabilitation after acute infarction can promote functional recovery.The LI of the affected hand reflects cerebral plasticity during rehabilitation after acute cerebral infarction.%目的 利用血氧水平依赖性功能磁共振成像(BOLD-fMRI)技术观察脑梗死急性期患者短期康复治疗前、后的手运动中枢激活区偏侧化指数(LI)的变化规律,探讨脑梗死患者急性期手运动功能康复的机制.方法 选取脑梗死急性期患者16例(

  16. 地西泮预处理对缺氧小鼠脑皮质硫化氢含量的影响%Effect of pretreatment with diazepam on content of H2S in mice cortex underwent cerebral hypoxia

    Institute of Scientific and Technical Information of China (English)

    倪云成; 汪燕; 张云倩; 马黎娜; 金培培; 许鹏程

    2013-01-01

    Objective To observe the effect of pretreatment with diazepam on the content of H2S in adult mice cortex underwent cerebral hypoxia.Methods Eighty Kunming adult mice were equally randomized into 5 groups of C (blank control),H (hypoxia model control),D4,D8 and D16(injected intraperitoneally with diazepam 4,8 and 16mg/kg at 30minutes before hypoxia,respectively).Hypoxia model was established by atmospheric hypoxia method.The occurrence time of mouth breathing was recorded.All mice were sacrificed at 24 h after hypoxia for determining the contents of water in brain tissue and H2S in the cortex.Results Compared with group H,the occurrence time of mouth breathing was prolonged and the content of water in brain was decreased in groups of D4,D8 and D16(P<0.05),the content of H2 S in the cortex was increased in group D16 (P<0.05).Conclusion Pretreatment of diazepam 16 mg/kg is helpful in protecting brain tissue from further hypoxia damage by increasing the release of H2S.%目的 观察地西泮预处理对缺氧小鼠脑皮质硫化氢(H2S)含量的影响.方法 80只昆明种小鼠随机均分为五组.其中的四组采用常压缺氧方法建立缺氧模型,分为单纯缺氧组和缺氧前30 min分别腹腔注射地西泮4、8、16 mg/kg三个预处理组(D4组、D8组、D16组);对照组不做任何处理.记录各组小鼠缺氧后出现张口呼吸的时间.24 h后将各组小鼠断头取脑,分别测定脑含水量和皮质中H2S的含量.结果 与单纯缺氧组比较,D4、D8、D16组出现张口呼吸的时间延长(P<0.05),脑含水量降低(P<0.05),D16组脑皮质H2S含量升高(P<0.05).结论 地西泮16mg/kg预处理可以促进缺氧小鼠脑皮质H2S生成,对缺氧脑损伤起保护作用.

  17. The discovery of motor cortex and its background.

    Science.gov (United States)

    Gross, Charles G

    2007-01-01

    In 1870 Gustav Fritsch and Edvard Hitzig showed that electrical stimulation of the cerebral cortex of a dog produced movements. This was a crucial event in the development of modern neuroscience because it was the first good experimental evidence for a) cerebral cortex involvement in motor function, b) the electrical excitability of the cortex, c) topographic representation in the brain, and d) localization of function in different regions of the cerebral cortex. This paper discusses their experiment and some developments in the previous two centuries that led to it including the ideas of Thomas Willis and Emanuel Swedenborg, the widespread interest in electricity and the localizations of function of Franz Joseph Gall, John Hughlings Jackson, and Paul Broca. We also consider the subsequent study of the motor cortex by David Ferrier and others.

  18. Malaria cerebral Cerebral malaria

    OpenAIRE

    Carlos Hugo Zapata Zapata; Silvia Blair Trujillo

    2003-01-01

    La malaria Cerebral (MC) es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1) citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2) formación de rosetas y aglutinación de glóbulos rojos parasitados; 3) producción de citoqu...

  19. Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

    Directory of Open Access Journals (Sweden)

    Hyoung-Seok Yun

    2001-02-01

    Full Text Available In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

  20. Influence of Electroacupuncture on the Expressions of BDNF and TrkB in Ischemic Cortex of Rats With Local Cerebral Ischemia%电针对局灶性脑缺血模型大鼠皮层BDNF、TrkB的影响

    Institute of Scientific and Technical Information of China (English)

    王彦春; 陈剑明; 梁少荣; 马骏; 甘水咏; 王述菊; 姜拯坤; 雷俊; 王培峻; 许永海

    2012-01-01

    Objective: To observe the influence of dectroacupuncture( EA)on the expressions of BDNF and its receptor TrkB in ischemic cortex of rats with local cerebral ischemia. Methods : The model of focal cerebral ischemia was set up by blocking up the middle cerebral artery(MCA) with filament in rats. The expressions of BDNF and TrkB positive neurons in ischemic cortex was observed with the method of immunocytochemistry SABC. Results: BDNF and TrkB positive neurons were mainly distributed in cortex around the ischemic focus. In pseudo - operation groups ,BDNF and TrkB positive neurons were few and low - expression in identical area. The expressions of BDNF and TrkB around ischemic cortex of model groups were significantly higher than that of pseudo - operation group( P < 0. 05); BDNF and TrkB positive neurons in EA group were more than that of model group(P<0. 05). Conclusion ;EA at Fengfu has a protective effect on ischemic brain injury by increasing the BDNF and its receptor TrkB expressions in cortex around the ischemic focus.%目的:观察电针对不同时间点局灶性脑缺血模型大鼠缺血区皮层BDNF、TrkB的影响.方法:采用线栓改良法复制大脑中动脉缺血模型(MCAO),采用免疫组化SABC法观察缺血皮层BDNF、TrkB表达情况.结果:BDNF、TrkB阳性神经元主要分布在梗死灶周围皮质区.假手术组大鼠相应区域可见少量阳性神经元表达,且强度较弱;模型组各时间点梗死周围皮质BDNF、TrkB阳性神经元比假手术组明显增多,差异有统计学意义(P<0.05);电针组各时间点梗死周围皮质BDNF、TrkB比相同时间点模型组显著增多,差异有统计学意义(P<0.05).结论:电针风府穴可以增加急性脑缺血后缺血周围皮质BDNF、TrkB阳性神经元,对缺血性脑损伤起修复和保护作用.

  1. Expression of Bcl-2 and Bax in Cerebral Cortex of Sodium Valproate Induced Autism Rats%丙戊酸钠诱导孤独症模型大鼠皮层Bcl-2、Bax的表达①

    Institute of Scientific and Technical Information of China (English)

    姜志梅; 崔利军; 郭津; 张士岭; 郭岚敏

    2013-01-01

    Objective To explore the role of Bcl-2 and Bax in pathogenesis of the autism. Methods Female Sprague-Dawley rats were given a single intraperitoneal injection of sodium valproate (VPA, 600 mg/kg) on 12.5 d after pregnancy, their offspring were as the model group;while the other pregnancy rats were given normal saline, their offspring were as the control group. Both groups were observed with the Nissl staining, immunohistochemistry of Bcl-2 and Bax and image analysis 1 d, 7 d, 14 d, 28 d, 56 d after birth. Results Compared with the control group, Nissl staining showed the number of cortical neurons decreased on 1 d and 7 d after birth in the model group, rapidly in-creased on 14 d after birth, and maintained in high level on 28d , 56 d after birth. For immunohistochemistry, the integrated optical density (IOD) of Bcl-2 and Bax decreased in cortex on 1~14 d after birth (P0.05). Com-pared with the control group, the IOD of Bcl-2 decreased much more at every time point (P0.05). The ratio of Bcl-2/Bax was the most on 1 d af-ter birth, and then decreased to approximately 1 in the control group, while it was the least on 7 d, most on 14 d, and decrease to less than 1 28 d after birth. Conclusion Apoptosis of cerebral cortex neurons increases in the autism model rats, especially in the early time.%  目的探讨Bcl-2、Bax在孤独症发病中的作用。方法孕12.5 d Sprague-Dawley孕鼠腹腔注射丙戊酸钠600 mg/kg建立子代孤独症模型大鼠,对照组注射同等剂量生理盐水。利用尼氏染色、免疫组化和图像分析技术观察比较出生后1 d、7 d、14 d、28 d和56 d两组大鼠脑部Bcl-2、Bax表达。结果尼氏染色:出生后1 d、7 d模型组神经元数量较少,出生14 d后剧增,出生后28 d、56 d仍高于对照组。免疫组化:出生后1~14 d两组Bcl-2、Bax表达均显著升高(P0.05);与对照组相比,模型组各日龄大鼠Bcl-2表达水平均显著降低(P0.05)。对照组Bcl-2/Bax值出生后1 d

  2. Ataque cerebral

    OpenAIRE

    Takeuchi Tan, Yuri; Fundación Valle de Lili

    1998-01-01

    ¿Qué es un ataque cerebral?/¿Qué tipos de ataque cerebral existen?/¿Cuáles son los síntomas de un ataque cerebral?/Factores de riesgo para un ataque cerebral/Tratamiento médico del ataque cerebral/¿por qué es importante acudir temprano cuando se presentan las señales de alarma?/ Manejo preventivo del ataque cerebral isquémico/Tratamiento quirúrgico del ataque cerebral/Enfermedad vascular cerebral hemorrágica/¿Cómo está constituido el grupo de ataque cerebral de la fundación Clínica Valle d...

  3. Ataque cerebral

    OpenAIRE

    Takeuchi Tan, Yuri; Fundación Valle de Lili

    1998-01-01

    ¿Qué es un ataque cerebral?/¿Qué tipos de ataque cerebral existen?/¿Cuáles son los síntomas de un ataque cerebral?/Factores de riesgo para un ataque cerebral/Tratamiento médico del ataque cerebral/¿por qué es importante acudir temprano cuando se presentan las señales de alarma?/ Manejo preventivo del ataque cerebral isquémico/Tratamiento quirúrgico del ataque cerebral/Enfermedad vascular cerebral hemorrágica/¿Cómo está constituido el grupo de ataque cerebral de la fundación Clínica Valle d...

  4. Effects of sevoflurane and isoflurane on proliferation of neural stem cells in rat cerebral cortex%七氟醚和异氟醚对大鼠大脑皮质神经干细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    林函; 刘劲; 李纯; 王佩芳; 高雅静; 马晓晓; 王春满; 梅虹霞; 连庆泉

    2013-01-01

    Objective To evaluate the effects of sevoflurane and isoflurane on the proliferation of neural stem cells in rat cerebral cortex.Methods The neural stem cells were isolated from Sprague-Dawley rats at 15 days of gestation and cultured at a density of (1-2) × 106 cells/ml.The cells of 3rd generation were seeded in 6-well plates coated with poly-lysine and randomly divided into 3 groups (n =24 wells each) using a random number table:control group (group C),sevoflurane group (group S) and isoflurane group (group Ⅰ).In S and Ⅰ groups,the cells were exposed to 4.9% sevoflurane and 2.8% isoflurane in a mixture of 5% CO2-95% O2 for 6 h,respectively.The cells were exposed to a mixture of 5 % CO2-95 % O2 for 6 h in group C.After 6 h of exposure,the plates were removed and the cells were continuously incubated for 2 h in an incubator at 37 ℃.The proliferation of cells was detected by immunocytochemistry and microplate method.The expression of proliferation-related genes such as signal transducers and activators of transcription 3 (STAT3),Sox2,Notchl and P21 mRNA was detected using quantitative real-time PCR.The expression of total STAT3 protein and phosphorylated STAT3 protein (p-STAT3) was determined using Western blot.Results Compared with C group,the rate of proliferation was significantly decreased,and the expression of p-STAT3 was down-regulated in I and S groups,and the expression of STAT3 mRNA was down-regulated in Ⅰ group (P < 0.05),and no significant change was found in the expression of STAT3 mRNA in S group (P > 0.05).There was no significant difference in the expression of Sox2,Notch1 and P21 mRNA and total STAT3 protein between the three