Biblioteca Digital de Teses e Dissertações PÓS-GRADUAÇÃO SCTRICTO SENSU Programa de Pós-Graduação em Ciências Fisiológicas
Use este identificador para citar ou linkar para este item: http://bdtd.uftm.edu.br/handle/tede/790
Registro completo de metadados
Campo DCValorIdioma
dc.creatorSOUZA, Rafael Rodrigues de-
dc.creator.ID09610463661por
dc.creator.Latteshttp://lattes.cnpq.br/0681676239903772por
dc.contributor.advisor1MARTINS, Antonio Roberto-
dc.contributor.advisor1ID74704516849por
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/3329015374505191por
dc.date.accessioned2019-07-23T14:12:51Z-
dc.date.issued2015-10-29-
dc.identifier.citationSOUZA, Rafael Rodrigues de. Expressão da sintase neuronal do óxido nítrico na displasia cortical focal tipo Taylor. 2015. 45f. Dissertação (Mestrado em Ciências Fisiológicas) - Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.por
dc.identifier.urihttp://bdtd.uftm.edu.br/handle/tede/790-
dc.description.resumoDisplasias corticais focais (FCDs) são caracterizadas por uma desorganização focal da estrutura normal do córtex cerebral, as quais são malformações causadas por anormalidades no desenvolvimento cortical (MCDs). FCD IIb ou displasia cortical focal tipo Taylor, estudada nesse trabalho, se caracteriza pela desorganização das camadas corticais e pela presença de Balloon cells (BCs) e neurônios dismórficos (DNs). Tais anormalidades são encontradas em pacientes com epilepsia resistentes ao tratamento medicamentoso, resultando no aumento do número de pacientes candidatos ao tratamento cirúrgico. A epileptogenicidade nas FCDs tem sido descrita como um desequilíbrio entre o balanço excitação-inibição. As propriedades do óxido nítrico (NO) tornam-no um candidato em potencial para participar do balanço excitação-inibição. O NO é um gás difusível, radical livre hidrofóbico que pode permear membranas celulares. A avaliação de cada paciente incluiu história clínica detalhada e exames neurológicos, tais como: eletroencefalograma (EEG) interictal/ictal, monitoramento interictal/ictal por vídeo-EEG, extensa bateria de testes neuropsicológicos e registros corticais intra-operatórios. Os córtices provenientes do processo cirúrgico foram estudados usando rotinas de coloração (H&E, cresil de violeta e impregnação por prata pelo método de Bielschowsky). A expressão de óxido nítrico sintase neuronal (nNOS), marcador de neurofilamento pan-neuronal (SMI311), proteína acídica fibrilar glial (GFAP), foi detectada utilizando anticorpos específicos através de técnicas de imunohistoquimíca. Foram estudados 23 pacientes com FCD IIb. As lesões epileptogênicas nos pacientes FCD foram amplamente distribuídas nas diversas regiões corticais. Displasia cortical, BCs e DNs foram encontrados em todos os 23 pacientes estudados. Neurônios hipertróficos (HNs), DNs, e BCs expressaram nNOS com intensidade variável. Célula bipolar, multipolar e inter neurônios sem nome específico foram observados com imunomarcação positiva para nNOS. Longos processos varicosos foram observados em todos os casos de FCD IIb. Em alguns casos com intensidade variada, a expressão de nNOS em núcleos ocorreu aparentemente na maioria dos tipos neuronais. A marcação de ambos, citoplasma e núcleos, em balloon cells foi variável. A expressão de nNOS em diferentes tipos de células e estruturas celulares do neocórtex com displasia cortical focal IIb, representa uma primeira abordagem para a identificação de uma base celular para compreender o envolvimento de nNOS na patogênese das crises epilépticas nesta doença.por
dc.description.abstractFocal cortical dysplasias (FCDs) are characterized by a focal disorganization of the normal structure of the cerebral cortex, which has been ascribed to malformations of cortical development (MCD). Focal cortical dysplasia type IIb or Taylor type, studied here, is characterized by the loss of cortical organization, dysmorphic neurons (DNs) and balloon cells (BCs). Patients with the disturbance presented drug-resistant epilepsy that underwent surgical resection of the epileptogenic region for the treatment of epilepsy. Epileptogenicity in FCD has usually been ascribed to a disturbance(s) of the excitation-inhibition balance. The properties of nitric oxide (NO) make it a putative candidate to participate in excitationinhibition balance. NO is a hydrophobic, freely diffusible radical gas that can permeate cell membranes. Patients evaluation included a detailed history and neurologic examination, interictal-ictal scalp EEG, interictal/ictal video-EEG monitoring, an extensive neuropsychological test battery and intra-operative cortical recording. The resected cortexes were studied using routine stains (H&E, cresyl violet and silver impregnation by the Bielschowsky method. Neuronal NOS (nNOS), pan-neuronal neurofilament marker (SMI311) and glial fibrillary acidic protein (GFAP) expressions were detected using specific antibodies in immunohistochemistry. We studied 23 patients presenting FCD IIb. The epileptogenic lesions in FCD patients were widely distributed over diverse cortical regions. Cortical dysplasia, BCs and DNs were found in all twenty-three patients. Hypertrophic, and dysmorphic neurons, and balloon cells expressed nNOS with variable intensity. Bipolar, multipolar or unnamed interneurons were found to stain for nNOS. Long varicose processes were observed in all FCD IIb cases. In some cases there was a variable intensity, nuclear expression of nNOS, apparently in most neuron types. Staining of both cytoplasm and nucleus of BCs was variable. The expression nNOS in different cell types and cellular structures of neocortex were detected in patient with focal cortical dysplasia IIb.eng
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superiorpor
dc.formatapplication/pdf*
dc.thumbnail.urlhttp://bdtd.uftm.edu.br/retrieve/5124/Dissert%20Rafael%20R%20Souza.pdf.jpg*
dc.languageporpor
dc.publisherUniversidade Federal do Triângulo Mineiropor
dc.publisher.departmentInstituto de Ciências da Saúde - ICS::Curso de Medicinapor
dc.publisher.countryBrasilpor
dc.publisher.initialsUFTMpor
dc.publisher.programPrograma de Pós-Graduação em Ciências Fisiológicaspor
dc.relation.referencesAlderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J, 357: 593–615. Andre VM, Wu N, Yamazaki I et al (2007) Cytomegalic interneurons: a new abnormal cell type in severe pediatric cortical dysplasia. J Neuropathol Exp Neurol 66: 491-504. Aoki C, Rhee J, Lubin M, Dawson TM (1997) NMDA – R1 subunit of the cerebral cortex colocalizes with neuronal oxide synthase at pre – and post synaptic sites and spines. Brain Research, 750: 25-40. Aquilano K, Baldelli S, Ciriolo MR (2014) Nuclear Recruitment of Neuronal Nitric-oxide Synthase by α-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis. The Journal of Biological Chemistry, 289: 365-378. Babbedge RC, Bland-Ward SL, Hart SL, Moore PK (1993) Inhibition of rat cerebellar nitric oxide synthase by 7 nitroindazole and related substituted indazoles. Br J Pharmacol, 110: 225–228. Barkovich J, Kuzniecky R, Dobyns W, Jackson G, Becker L, Evrard P (1996) A classification scheme for malformations of cortical development. Neuropediatrics, 27:59-63. Barkovich AJ, Gerrini R, Kuzniecky RI, Jackson GD, Dobyns WB (2009) A development and genetic classification for malformations of cortical development: update 2012. Brain 135: 1348-1369. Bear MF, Kirkwood A. (1993) Neocortical long-term potentiation. Curr Opin Neurobio, 3(2):197-202. Bentivoglio M, Tassi L, Pech E, Costa C, Fabene PF, Spreafico R (2003) Cortical development and focal cortical dysplasia. Epileptic Disord, 5:27–34. Blumcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, Becker A, Cepeda C, Cendes F, Colombo N, Crino P, Cross JH, Delalande O, Dubeau F, Duncan J, Gerrini R, Kahane P, Mathern G, Najm I, Ozkara Ç, Raybaud C, Represa A, Roper SN, Salomon N, Schulze-Bonhage A, Tassi L, Vezzani A, Spreafico R (2011) The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52: 158-174. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, e Snyder SH (1991) Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron, 7: 615–624. Brenman JE, Chao DS, Gee SH, McGee AW, Craven, SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner, SC, Bredt DS (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell, 84: 757–767. Brenman JE, Bredt DS (1997) Synaptic signaling by nitric oxide. Curr Opin Neurobiol, 7: 374–378. Borowicz KK, Luszczki J, Kleinrok Z, Cuczwar SJ (2000) 7-nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions. J Neural Transm, 107: 1117–1126. Chamberlain WA, Prayson RA (2008) Focal cortical dysplasia type II (malformations of cortical development) aberrantly expresses apoptotic proteins. Appl Immunohistochem Mol Morphol 16: 471-476. Chang YE, Jakobi R, Mcginty A, Foschi J, Dunn MJ, Sorokin A (2000) Cyclooxygenase 2 promotes cell survival by stimulation of dynein light chain expression and inhibition of neuronal nitric oxide synthase activity. Molecular and Cellular Biology, 22: 8571–8579. Crane BR, Arvai AS, Ghosh DK, Wu C, Getzoff ED, Stuehr DJ, Tainer JA (1998) Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science, 279: 2121–2126. Crino PB, Duhaime C, Baltuch G, White R ( 2001) Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia. Neurology, 56: 906–913. Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder, SH (1993) Mechanisms of nitric oxide mediated neurotoxicity in primary brain cultures. J Neurosci, 13: 2651–2661. DeFelipe J (1993) A study of NADPH diaphorase-positive axonal plexuses in the human temporal cortex. Brain Res 615: 342-346. Dimmeler S, Zeiher AM (1997) Nitric oxide and apoptosis: another paradigm for the doubleedged role of nitric oxide. Nitric Oxide, 1: 275-81. Egberongbe YI, Gentleman SM, Falkai P, Bogerts B, Polak JM, Roberts GW (1994) The distribution of nitric oxide synthase immunoreactivity in the human brain. Neuroscience, 59: 561–578. Farrell MA, De Rosa MJ, Curran JG, Secor DL, Cornford ME, Comair YG, Peacock WJ, Shields WD, Vinters HV (1992) Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy. Acta Neuropathol, 83: 246 –259. Fauser S, Becker A, Schulze-Bonhage A, et al (2004) CD34 immunoreactive balloon cells in cortical malformations. Acta Neuropathol, 108:272-278. Fauser S, Huppertz HJ, Bast T, et al (2006) Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in series of 120 patients. Brain, 129: 1907–1916. Fertuzinhos S, Krsnik Z, Kawasawa YI, Rasin MR.; Kwan KY, Chen JG, Judas M, Hayashi M, Sestan N (2009) Selective depletion of molecularly defined cortical interneurons in human holoprosencephaly with severe striatal hypoplasia. Cereb Cortex, 19; 2196-2207. Forstermann U, Closs EI, Pollock JS, Nakane M, Schawarz P, Gath I, Kleinert H (1994) Nitric oxide synthase isozymes: characterization, purification, molecular cloning, and functions. Hypertension, 23: 1121-31. Forstermann U, Mulsch A, Bohme E, Busse R (1986) Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries. Circ Res, 58: 531–538. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. European. Heart Journal, 33: 829–837. Furchgott RF, Cherry PD, Zawadzki JV, Jothianandan D (1984) Endothelial cells as mediators of vasodilation of arteries. J Cardiovasc Pharmacol, 53: 557–573. Garthwaite J (2008) Concepts of neural nitric oxide-mediated transmission. European Journal of Neuroscience, 27: 2783–2802. Garthwaite G, Bartus K, Malcolm D, Goodwin DA, Kollb-Sielecka M, Dooldeniya C, Garthwaite J. (2006) Signaling from blood vessels to CNS axons through nitric oxide. J. Neurosci, 26: 7730–7740. Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature, 336: 385–388. Gibb BJ, Garthwaite J (2001) Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain. European Journal of Neuroscience, 13: 539–544. Guerrini R, Dobyns WB (2014) Malformations of cortical development: clinical features and genetic causes. Lancet Neurol, 13: 710-726. Guerrini R, Dobyns W, Barkovich A (2008) Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment options. Trends Neurosci, 31: 154– 162. Guerrini R, Parrini E (2010) Neuronal migration disorders. Neurobiol Dis 38: 154-166. Griffith OW, Stuehr DJ (1995) Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol, 57: 707–36. Gillardon F., H. Krep, G. Brinker, C. Lenz, B. Bottiger, and K.-A. Hossmann. (1998) Induction of protein inhibitor of neuronal nitric oxide synthase/ cytoplasmic dynein light chain following cerebral ischemia. Neuroscience, 84: 81–88. González-Martínez JÁ, Moddel G, Ying Z et all; (2009) Neuronal nitric oxide synthase expression in resected epileptic dysplastic neocortex. J Neurosurg, 110: 343–349. Hannan AJ, Servottes S, Katsnelson A, Sisodiya S, Blakemore C, Squier M, and Molnár Z (1999) Characterization of nodular neuronal heterotopia in children. Brain, 122: 219-238. Hardiman O, Burke T, Phillips J, Murphy S, O’Moore B, Staunton H, Farrell MA (1988) Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy. Neurology, 38: 1041–1047. Hardingham N, Dachtle J, Fox k (2013) The role of nitric oxide in pre-synaptic plasticity and homeostasis. Frontiers in Cellular Neuroscience, 7: 1–19. Jaffrey SR, Snyder SH (1996). PIN: an associated protein inhibitor of neuronal nitric oxide synthase. Science, 274: 774–777. Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science, 274: 1133- 1138. Kwan KY, Lan MMS, Johnson MB et al. (2012) Species- dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell, 149: 899-911. Kiss JP, Vizi ES (2001) Nitric oxide: a novel link between synaptic and nonsynaptic transmission. Trends Neurosci, 24: 211–215. Kuzniecky R, Garcia J, Faught E, Morawetz R (1991) Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Ann Neurol, 29: 293–298. Kuzniecky RL and Jackson GD (2008) Malformations of cortical development. In: Epilepsy, Jerome Engel Jr. and Timothy A Pedley, Eds. Lippincott Williams & Wilkins, Philadelphia, USA. Korzhevskii DE, Otellin VA, Grigorev IP, Petrova ES, Gilerovich EG, Zin'kova NN (2008) Immunocytochemical detection of neuronal NO synthase in rat brain cells. Neurosci.Behav.Physiol 38: 835-838. Lamparello P, Baybis M, Polland J, et al (2007) Developmental lineage of cells types in cortical dysplasia with balloon cells. Brain, 130: 2267–2276. Leite JP, Chimelli L, Terra-Bustamante VC, Costa ET, Assirati JA, Nucci deG, Martins AR (2002) Loss and Sprouting of Nitric Oxide Synthase Neurons in the Human Epileptic Hippocampus. Epilepsia, 43: 235–242. Lent R (2010) Cem bilhões de neurônios. Conceitos fundamentais de neurociência. SP, Atheneu. Luo CX, Zhu DY (2011) Research progress on neurobiology of neuronal nitric oxide synthase. Neurosci Bul, 27: 23-35. Lois C, Verdugo JMG, Buylla AA (1996) Chain migration of neuronal Precursors. Science, 271: 978-981. MacMicking J, Xie QW, Nathan C (1997) Nitric oxide and macrophage function. Annu Rev Immunol, 15: 323–350. Madhusoodanan KS, Murad F (2007) NO- cGMP signaling and regenerative medicine involving stem cells. Neurochem Res, 32: 681-94. Martinian L, Boer K, Middeldorp J, et al (2009) Expression patterns of glial ifibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies. Neuropathol appl Neurobiol, 35: 394–405. Martins AR, Zanella CAB, Zucchi FCR, Dombroski TCD, Costa ET, Guethe LM, Oliveira AO, Donatti ALF, Neder L, Chimelli L, De Nucci G, Lee-Ho P, Murad F (2011) Immunolocalization of nitric oxide synthase isoforms in human archival and rat tissues, and cultured cells. J. Neurosci Methods, 198: 16-22. Martins AR, Dias MM, Vasconcelos TM et al.(1999) Microwave-stimulated recovery of myosin-V immunoreactivity from formalin-fixed, paraffin-embedded human CNS. J Neurosci Methods, 92: 25-29. Mendes RV, Martins AR, De,Nucci G, Murad F, Soare FA (2001) Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma. Histopathology, 39: 172-178. Najm IM, Ying Z, Babb T, Mohamed A, Hadam J, LaPresto E, et al (2000) Epileptogenicity correlated with increased N-methyl- D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia. Epilepsia, 41: 971–976. Noble MA, Munro AW, Rivers SL, Robledo L, Daff SN, Yellowlees LJ, Shimizu T, Sagami I, Guillemette JG, Chapman SK (1999) Potentiometric analysis of the flavin cofactors of neuronal nitric oxide synthase. Biochemistry, 38: 16413–16418. Ohyu J, Takashima S (1998) Developmental characteristics of neuronal nitric oxide synthase (nNOS) immunoreactive neurons in fetal to adolescent human brains. Brain Res, 110:193– 202. Palmini A (2000) Disorders of cortical development. Curr Opin Neurol, 13: 183-192. Palmini A, Andermann E, Andermann F (1994) Prenatal events and genetic factors in epileptic patients with neuronal migration disorders. Epilepsia, 35: 965-973. Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV (2004) Terminology and classification of the cortical dysplasias. Neurology, 62: 52-58. Rakic P (1988) Specification of cerebral cortical areas. Science, 241: 170-176. Rakic P (1990) Principles of neural cell migration. Experientia, 46: 882-891. Rakic P (1995) A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci, 18: 383-388. Rakic P (2007) The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering. Brain Research Reviews 55: 204-219. Rapoport RM, Draznin MB, Murad F (1983) Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation. Nature, 306: 174– 176. Schuman EM, Madison DV (1994) Nitric oxide and synaptic function. Journal of Neuroscience, 17: 153–183. Schmidt HH, Gagne GD, Nakane M, Pollock JS, Miller MF, Murad F (1992) Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J.Histochem.Cytochem. 40: 1439-1456. Shoo B, Jiang J, Wu Q, et al; (2011) The Nuclear Localization of CAPON in Hippocampus and Cerebral Cortex Neurons after Lipopolysaccharide Stimulation. Neuroimmunomodulation, 18: 89–97. Sisodiya SM, Fause S, Cross JH, Thom M (2009) Focal cortical dysplasia type II: biological features and clinical perspectives. Lancet Neurol 8: 830-843. Spreafico R, Blumcke I (2010) Focal Cortical Dysplasias: clinical implication of neuropathological classification systems. Acta Neuropathol. 120 (3): 359-367. Tassi L, Colombo N, Garbelli R, Francione S, La Russo G, Mai K, Cardinale F, Cossu M, Ferrario A, Galli C, Bramerio M, Criterio A, Spreafico R (2002) Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain, 125: 1719-32. Taylor DC, Falconer MA, Bruton CJ, Corsellis JA (1971) Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry, 34: 369-387. Valtschanoff JG, Weinberg RJ, Kharazia VN, Schmidt HHHW, Nakane M, Rustioni A (1993) Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunocytochemistry, and colocalization with GABA. Neurosci Lett 157:157–161. Ying Z, Gonzales–Martinez J, Tilelli C, Bingaman W, Najn I (2005) Expression of neural stem cell surface marker CD133 in balloon cells of human focal cortical dysplasia. Epilepsia, 46:1716–1723. Zhou L, Zhu D (2009) Neuronal nitric oxide synthase: structure, subcellular localization, regulation and clinical implications. Nitric oxide 20: 223-230.por
dc.rightsAcesso Abertopor
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectDisplasia cortical focal tipo IIb.por
dc.subjectÓxido nítrico sintase neuronal.por
dc.subjectNeurônios dismórficos.por
dc.subjectBalloon cells.por
dc.subjectEpilepsia.por
dc.subjectFocal cortical dysplasia type IIb.eng
dc.subjectNeuronal nitric oxide synthase.eng
dc.subjectDysmorphic neurons.eng
dc.subjectBalloon cells.eng
dc.subjectEpilepsy.eng
dc.subject.cnpqFisiologiapor
dc.subject.cnpqNeurofisiologiapor
dc.titleExpressão da sintase neuronal do óxido nítrico na displasia cortical focal tipo Taylorpor
dc.title.alternativeExpression of neuronal nitric oxide synthase in Taylor’s dysplasiaeng
dc.typeDissertaçãopor
Aparece nas coleções:Programa de Pós-Graduação em Ciências Fisiológicas

Arquivos associados a este item:
Arquivo Descrição TamanhoFormato 
Dissert Rafael R Souza.pdfDissert Rafael R Souza1,35 MBAdobe PDFThumbnail
Visualizar/Abrir


Este item está licenciada sob uma Licença Creative Commons Creative Commons