Epileptogenicity of neocortex in the novel rat model of focal cortical dysplasia

• Project/Area Number: 16590832
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: KYUSHU UNIVERCITY
• Principal Investigator: SHIGETO Hiroshi Kyushu University Hospital, Research Associate, 大学病院, 助手 (50335965)
• Co-Investigator(Kenkyū-buntansha): OHYAGHI Yasumasa Kyushu University Hospital, Assistant Professor, 大学病院, 講師 (30301336) ; 池添 浩二 九州大学, 大学病院, 講師 (80343317)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
• Keywords: Epilepsy / Focal cortical malformation / Neuronal migration disorder / Animal model / Kindling / 新皮質 / 皮質形成異常 / てんかん原性 / 神経新生 / Freeze lesion

Research Abstract

Focal cortical malformation is an important cause of intractable epilepsy in human. However, its in vivo epileptogenicity remains unclear. Freeze lesions postnatally introduced in the hindbrain of rodents produce extra-sulci and microgiri demonstrating only in vitro epileptogenicity. We, therefore, aimed to develop a prenatally introduced freeze lesion model and prove its in vivo epileptogenicity.
At 18 days post-conception, a metal probe cooled by liquid nitrogen was placed on the left scalp of a Sprague-Dawley rat embryo, through the uterus wall. After birth, electrical kindling stimulation was applied on between the right fronto-medial and fronto-lateral points on the frontal lobe of rat pups, and threshold and duration of afterdischarges (ADs) were measured from 0 to 40 days. Brain tissues from electrically stimulated and unstimulated animals were immunohistochemically examined.
The freeze lesion rats developed significantly longer ADs in the cortex and hippocampus compared to the sham operated and control animals, and acquired hippocampal kindling earlier after electrical stimulation although spontaneous seizure was not revealed. Brains from freeze lesioned rats displayed severe disorganization of cortical layers with ramdamly oriented dendrites and axons and nodular heterotopia in the cortical layer and/or the subcortical white matter. Immunoreactivities for N-methyl-D-aspartate receptor subunits 1, 2B and glutamate/aspartate transporter stainings were significantly enhanced by the semi-quantitative densitometry in the lesion, which was markedly potentiated by electrical stimulation.
Freeze lesion created during the late embryonic stage induces focal cortical malformation with neuronal migration abnormality, which exhibits in vivo epileptogenicity on electrical stimulation.

Research Products

• [Journal Article] A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene. (2006)
  • Author(s): Furuya H, Murai H, Takasugi K, Ohyagi Y, Urano F, Kishi T, Ichinose H, Kira J.
  • Journal Title: Clin Neurol Neurosurg 108 Pages: 784-6
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Motor neuron disorder simulating ALS induced by chronic inhalation of pyrethroid insecticides. (2006)
  • Author(s): Doi H, Kikuchi H, Murai H, Kawano Y, Shigeto H, Ohygai Y, Kira J.
  • Journal Title: Neurology 67 Pages: 1894-1985
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional network of the basal ganglia and cerebellar motor loops in vivo : different activation patterns between self-initiated and externally triggered movements. (2006)
  • Author(s): Taniwaki T, Okayama A, Yoshiura T, Togao O, Nakamura Y, Yamasaki T, Ogata K, Shigeto H, Ohyagi Y, Kira J, Tobimatsu S.
  • Journal Title: Neuroimage 31 Pages: 745-53
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene. (2006)
  • Author(s): Furuya H, Murai H, Takasugi K, Ohyagi Y, Urano F, Kishi T, Ichinose H, Kira J.
  • Journal Title: Clin Neurol Neurosurg. 108 Pages: 784-6
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Motor neuron disorder simulating ALS induced by chronic inhalation of pyrethroid insecticides. (2006)
  • Author(s): Doi H, Kikuchi H, Murai H, Kawano Y, Shigeto H, Ohyagi Y, Kira J.
  • Journal Title: Neurology 67 Pages: 1894-1985
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional network of the basal ganglia and cerebellar motor loops in vivo : different activation patterns between self-initiated and externally triggered movements. (2006)
  • Author(s): Taniwaki T, Okayama A, Yoshiura T, Togao 0, Nakamura Y, Yamasaki T, Ogata K, Shigeto H, Ohyagi Y, Kira J, Tobimatsu S.
  • Journal Title: Neuroimage. 31 Pages: 745-53
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A case of adult-onset Sydenham chorea accompanied with psychiatric symptoms (2006)
  • Author(s): Kin S, Taniwaki T, Shigeto H, Nomura T, Ohyagi Y.
  • Journal Title: No To Shinkei 58 Pages: 155-159
• [Journal Article] Functional network of the basal ganglia and cerebellar motor loops in vivo : Different activation patterns between self-initiated and externally triggered movements. (2006)
  • Author(s): Taniwaki T, Okayama A, Yoshiura T, Togao O, Nakamura Y, Yamasaki T, Ogata K, Shigeto H, Ohyagi Y, Kira JI, Tobimatsu S.
  • Journal Title: Neuroimage Feb(E pub ahead)
• [Journal Article] Some flavonoids and DHEA-S prevent the cis-effect of expanded CTG repeats in a stable PC12 cell transformant. (2005)
  • Author(s): Furuya H, Shinnoh N, Ohyagi Y, Ikezoe K, Kikuchi H, Osoegawa M, Fukumaki Y, Nakabeppu Y, Hayashi T, Kira J.
  • Journal Title: Biochem Pharmacol 69 Pages: 503-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Some flavonoids and DHEA-S prevent the cis-effect of expanded CTG repeats in a stable PC12 cell transformant. (2005)
  • Author(s): Furuya H, Shinnoh N, Ohyagi Y, Ikezoe K, Kikuchi H, Osoegawa M, Fukumaki Y, Nakabeppu Y, Hayashi T, Kira J.
  • Journal Title: Biochem Pharmacol. 69 Pages: 503-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thalamic involvement of status epilepticus : Diffusion weighted image of MRI in two cases of status epilepticus. Unveiling the mystery of the brain-Neurophysiological investigation of the brain function. International congress series 1278 S. Tsuji, S. Tobimatsu et al. ed (2005)
  • Author(s): Shigeto H, Uehara T, Uchida K, Nomura T, Taniwaki T, Kira J.
  • Journal Title: Elsevier Amsterdam Pages: 193-196
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Relapsing Wernicke's encephalopathy after gastrectomy (2005)
  • Author(s): Arimura K, Murai H, Kikuchi H, Shigeto H, Taniwaki T, Furuya H, Kira J.
  • Journal Title: Nippon Naika Gakkai Zasshi 94(8) Pages: 1606-1608
  • NAID: 10016948355
• [Journal Article] A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene. (2005)
  • Author(s): Furuya H, Murai H, Takasugi K, Ohyagi Y, Urano F, Kishi T, Ichinose H, Kira J
  • Journal Title: Clin Neurol Neurosurg Nov(E pub ahead)
• [Journal Article] A patient with paraneoplastic limbic encephalitis induced by breast cancer presenting with hypersomnia (2005)
  • Author(s): Kawamura N, Kawajiri M, Ohyagi Y, Minohara M, Murai H, Kira J.
  • Journal Title: Rinsho Shinkeigaku 45(8) Pages: 575-578
• [Journal Article] Some flavonoids and DHEA-S prevent the cis-effect of expanded CTG repeats in a stable PC12 cell transformant. (2005)
  • Author(s): Furuya H, Shinnoh N, Ohyagi Y, Ikezoe K, Kikuchi H, Osoegawa M, Fukumaki Y, Nakabeppu Y, Hayashi T, Kira J.
  • Journal Title: Biochem Pharmacol 69(3) Pages: 503-516
• [Journal Article] Intracellular A beta 42 activates p53 promoter : a pathway to neurodegeneration in Alzheimer's disewase (2005)
  • Author(s): Ohyagi Y, Asahara H, Kira J, Tabira T
  • Journal Title: FASEB J 19 Pages: 255-257
• [Journal Article] A case of dermato-fasciitis : amyopathic dermatomyositis associated with fasciitis. (2004)
  • Author(s): Tsuruta Y, Ikezoe K, Nakagaki H, Shigeto H, Kawajiri M, Ohyagi Y, Kira J.
  • Journal Title: Clin Rheumatol 23 Pages: 160-162
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A case of dermato-fasciitis : amyopathic dermatomyositis associated with fasciitis. (2004)
  • Author(s): Tsuruta Y, Ikezoe K, Nakagaki H, Shigeto H, Kawajiri M, Ohyagi Y, Kira J.
  • Journal Title: Clin Rheumatol. 23 Pages: 160-162
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] High frequency direct cortical electrical stimulation : an animal model of induced acute focal seizures. Deep brain stimulation and epilepsy. Hans 0 Luders ed. (2004)
  • Author(s): Shigeto H, Najm I, Boongird A, Nair D, Burrier C, Baker K, Luders HO.
  • Journal Title: Martin Dunitz, London Pages: 97-101
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] High frequency direct cortical electrical stimulation : an animal model of induced acute focal seizures (2004)
  • Author(s): Shigeto H, Najm I, Boongird A, Luders HO
  • Journal Title: Deep Brain stimulation and epilepsy (Ed. Hans O Luders) 1 Pages: 97-101
• [Journal Article] Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy (2004)
  • Author(s): Ikezoe K, Nakagawa M, Osoegawa M, Kira J, Nonaka I
  • Journal Title: Acta Neuropathol 107 Pages: 439-442
• [Book] Thalamic involvement of status epilepticus : Diffusion weighted image of MRI in two cases of status epilepticus. Unveiling the mystery of the brain - Neurophysiological investigation of the brain function. International congress series 1278 S. Tsuji, S. Tobimatsu et al. ed (2005)
  • Author(s): Shigeto H, Uehara T, Uchida K, Nomura T, Taniwaki T, Kira J.
  • Publisher: Elsevier Amsterdam
  • Description: 「研究成果報告書概要(和文)」より
• [Book] High frequency direct cortical electrical stimulation : an animal model of induced acute focal seizures. Deep brain stimulation and epilepsy. Hans O Luders ed. (2004)
  • Author(s): Shigeto H, Najm I, Boongird A, Nair D, Burrier C, Baker K, Luders HO.
  • Publisher: Martin Dunitz, London
  • Description: 「研究成果報告書概要(和文)」より