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A study on the molecular pathomechanisms underflying intractable epilepsy

Research Project

Project/Area Number 12470287
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

TAKAHASHI Hitoshi  NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (90206839)

Co-Investigator(Kenkyū-buntansha) TANAKA Ryuichi  NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (30018816)
NAWA Hiroyuki  NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (50183083)
KAKITA Akiyoshi  NIIGATA UNIVERSITY Brain Research Institute, Associate professor, 脳研究所, 助教授 (80281012)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsIntractable epilepsy / Neuropathology / Molecular pathology / Gene analysis / DNA array / Brain developmental error / Cortical dysplasia / Neurosurgery for epilepsy / Bilateral periventricular nodular heterotopia / Migration disorder / 剖検例 / DNA macroarray / 結節性硬化症 / hamartin / tubelin
Research Abstract

1. We carried out the histopathological observations in 125 patients with pharmacoresistant intractable epilepsy. Cortical dysplasia (Grade I) in the medial temporal lobe was found to be the most frequent abnormality (66 cases). The mean ages at onset of seizure and at surgery were 12.2 years and 31.4 years, respectively. In all the cases, glial fibrillary acidic protein-positive reactive astrocytes were present in the affected cortex as well as in the subcortical white matter. The hippocampus was examined in a total of 32 cases : there were no correlation between histological severity of hippocampal sclerosis and that of cortical dysplasia.
2. We reported the histopathological features of an autopsy case of bilateral periventricular nodular heterotopia with widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex, in whom we found a novel exon 11 (Val528Met) filamin 1 mutation.
3. We employed the DNA array technique to compare the mRNA expression profiles of three neocortical subregions of the human brain : prefrontal cortex (Area 46), motor cortex (Area 4) and visual cortex (Area 17). The macroarray analysis on high quality mRNA from postmortem brains revealed that the expression profiles of the different cortical areas are almost similar : only six out of 1088 known genes exhibited significant differences (>2-fold) in their expression. RT-PCR studies with an increased number of samples confirmed that expression of only two genes, annexin II and early growth response protein 1, varied by 2-fold among the regions, whereas exoression of the others showed large inter-individual difference. These results suggest that the whole neocortex of humans is more homogeneous than we expected at the level of gross gene expression profiles.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Hayashi, S.: "Ganglioglioma with a tanycytic ependymoma as the glial component"Acta Neuropathologica. 99. 310-316 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watakabe, A.: "Similarity and variation in gene expression among human cerebral cortical subregions by DNA macroarray : technical consideration of RNA expression profiling from postmortem samples"Molecular Brain research. 88. 74-82 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita, A.: "Experimentally induced leptomeningeal glioneuronal heterotopia and underlying cortical dysplasia of the lateral limbic area in rats treated transplacentally with methylmercury"Journal of Neuropathology and Experimental Neurology. 60. 768-777 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameyama, S.: "Surgical strategy and outcomes for epileptic patients with focal cortical dysplasia or dysembryoplastic neuroepithelial tumor"Epilepsia. 42(Suppl 6). 37-41 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oishi, M: "Fusiform gyrus epilepsy : the use of ictal magnetoencephalography"Journal of Neurosurgery. 97. 200-204 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada, A.: "Hemifacial spasm associated with an ependymal cyst in the cerebello-pontine angle"Journal of Neurosurgery. 97. 482-485 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita, A.: "Neuronal migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury"Acta Neuropathologica. 104. 409-417 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita, A.: "Bilateral periventricular nodular heterotopia due to filamin 1 gene mutation : widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex"Acta Neuropathologica. 104. 649-657 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita, A.: "Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere"Journal of Comparative Neurology. 458. 381-388 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita, A.: "Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury"Journal Neuropathology and Experimental Neurology. 42(Suppl 6)(In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高橋 均: "Pleomorphic xanthoastrocytoma"病理と臨床. 18. 1051-1055 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 柿田明美: "てんかんの病理 -外科手術標本にみられる大脳皮質形成異常所見 -"神経内科. 58. 155-161 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高橋 均: "脳病理学と脳疾患標本資源の重要性"学術月報. 56. 380-384 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi S: "Ganglioglioma with a tanycytic ependymoma as the glial component"Acta Neuropathol. 99. 310-316 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watakabe A: "Similarity and variation in gene expression among human cerebral coritical subregions by DNA macroarrays : technical consideration of RNA expression profiling from postmortem samples"Mol Brain Res. 88. 74-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Experimentally induced leptomeningeal glioneuronal heterotopia and underlying cortical dysplasia of the lateral limbic area in rats treated transplacentally with methylmercury"J Neuropathol Exp Neurol. 60. 768-777 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameyama S: "Surgical strategy and outcomes for epileptic patients with focal cortical dysplasia or dysembryoplastic neuroepithelial tumor"Epilepsia. 42 (Suppl 6). 37-41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oishi M: "Fusiform gyrus epilepsy : the use of ictal magnetoencephalography"J Neurosurg. 97. 200-204 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada A: "Hemifacial spasm associated with an ependymal cyst in the cerebello-pontine angle"J Neurosurg. 97. 482-485 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Neuronal migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury"Acta Neuropathol. 104. 409-417 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Bilateral periventricular nodular heterotopia due filamin 1 gene mutation : widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex"Acta Neuropathol. 104. 649-657 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere"J Comp Neurol. 458. 381-388 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury"J Neuropathol Exp Neurol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi H: "Pleomorphic xanthoastrocytoma"Byori To Rinsho. 18. 1051-1055 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakita A: "Surgical pathologic features of intractable epilepsy"Shinkeinaika. 58. 155-161 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi H: "Brain pathology and brain tissue resources for neuroscience."Gakujutsugeppo. 56. 380-384 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oishi, M.: "Fusiform gyrus epilepsy : the use of ictal magnetoencephalography"The Journal of Neurosurgery. 97. 200-204 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kakita, A.: "Bilateral periventricular nodular heterotopia due to filamin I gene mutation"Acta Neuropathologica. 104. 649-657 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 柿田 明美: "てんかんの病理-外科手術標本にみられる大脳皮質形咳異常-"神経内科. 58. 155-161 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kameyama, S.: "Surgical strategy and outcomes for epileptic patients with focal cortical dysplasia or dysembryoplastic neuroepithelial tumor"Epilepsia. 42(Suppl.6). 37-41 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe, A.: "Similarity and variation in gene expression among human cerebral cortical subregions revealed by DNA macroarrays : technical consideration of RNA expression profiling from postmortem samplesA"Malecular Brain Research. 88. 74-82 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watakabe,A.: "Similarity and variation in gene expression among human cerebral cortical subregions revealed by DNA macroarrays : technical consideration of RNA expression profiling from postmortem samples."Molecular Brain Research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi,S.: "Ganglioglioma with a tanycytic ependymoma as the glial component."Acta Neuropathologica. 99・3. 310-316 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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