自発てんかん発作を有した皮質異形成ラットモデル  [in Japanese] Spontaneous seizures in a rat models of multiple prenatal lesioning  [in Japanese]

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Abstract

局所皮質異形成は,難治性てんかんとの強い関連が指摘されている.われわれは,胎児期に頭蓋へ多発性の凍結損傷を与え,大脳皮質に皮質異形成を作製したラットモデルを作製し,自発てんかん発作を発症するかどうかを観察した.胎児期に皮質異形成を両側の前頭頭頂葉に作製したラットにて,出生後海馬にて自発てんかん発作波が観察され,臨床的にもヒトの側頭葉てんかんに類似したものであった.皮質異形成部と海馬での免疫組織化学的検討にて,てんかん原性の獲得の過程でグルタミン酸受容体を介した興奮性の変化がみられた.このモデルは,ヒトのてんかん原性獲得の機序を明らかにする手がかりを有すると考えられる.

Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Eleven of 16 rats showed spontaneous seizures arising in the hippocampus from postnatal day47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. Alterations in the levels of glutamatergic and GABA-ergic receptors were investigated during growth. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. This model should enable better clarification of the mechanisms underlying the development of human epilepsy.

Journal

  • Rinsho Shinkeigaku

    Rinsho Shinkeigaku 54(12), 1132-1135, 2014

    Societas Neurologica Japonica

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