| Project/Area Number |
16590832
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | KYUSHU UNIVERCITY |
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Principal Investigator |
SHIGETO Hiroshi Kyushu University Hospital, Research Associate, 大学病院, 助手 (50335965)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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