Neuropathological analysis on epileptogenesis of progressive myoclonic epilepsy

进行性肌阵挛癫痫发病的神经病理学分析

• 批准号: 14570792
• 负责人: HAYASHI Masaharu
• 金额: $ 1.73万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570792/
• 关键词: Progressive myoclonic epilepsy; Dentatorubropallidolusian atrophy; Immunohistochemistry; Neuronal ceroid-lipofuscinosis; Lafora disease; Calcium-binding proteins; Glutamate transporter; Oxidative stress; 進行性ミオクローヌスてんかん; 神経性セロイド・リポフスチノーシス; 酵素標識免疫

First, we immunohistochemically examined the expressions of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex of autopsy cases of hereditary dentatorubral-pallidoluysian atrophy (DRPLA), which is one of the important causes of progressive myoclonus epilepsy (PME) in Japan. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 and 2 cases of juvenile and early adult types with PME, 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to neurotransmitters, neuropeptides, calcium-binding proteins, and excitatory amino acid transporters. Although the size of the tegmentum was small, we failed to find any PME-specific brainstem changes in the expressions of neurotransmitters, neuropeptides and calcium-binding proteins. The numbers of interneurons immunoreactive for calbindin-D28K and parv … More albumin, which are speculated to be markers of GABAergic inhibitory interneurons, were reduced throughout the cerebral cortex predominantly in cases with PME. The expressions of glutamate transporters modifying glutamate excitotoxicity were comparatively spared. Similarly, four autopsy cases of neuronal ceroid-lipofuscinosis (NCL) showed the reduced expressions of calcium-binding proteins with preserved ones of glutamate transporter in the cerebral cortex. Regarding Lafora disease, we immunohistochemically examined neurodegeneration in three autopsy cases and evaluated oxidative products in urine and serum isolated from two patients using ELISA. Increased deposition of oxidative products to DNA and lipids were recognized in both the autopsy brains and urine specimens. Although the expression of glial glutamate transporter EAAT1 was comparatively preserved, that of another glial glutamate transporter EAAT2 was reduced in three autopsy cases, irrespective of occurrence of Lafora body. These findings suggest that different pathomechanisms seem to be related to epileptogenesis in each disorder causing PME. Less

首先，我们采用免疫组织化学方法检测了遗传性齿状核红斑-苍白球卢伊西亚萎缩症（DRPLA）尸检病例脑干和大脑皮层中神经递质、神经肽、钙结合蛋白和/或谷氨酸转运蛋白的表达，该病是日本进行性肌阵挛癫痫（PME）的重要原因之一。研究对象包括 14 例经临床病理证实的 DRPLA 病例，包括 7 例和 2 例伴有 PME 的青少年型和早期成年型，5 例不伴 PME 的成年晚期型，以及 10 例年龄匹配的对照。用神经递质、神经肽、钙结合蛋白和兴奋性氨基酸转运蛋白的抗体处理脑干和大脑皮层的连续切片。尽管被盖的尺寸很小，但我们未能在神经递质、神经肽和钙结合蛋白的表达中发现任何 PME 特异性脑干变化。钙结合蛋白-D28K 和小白蛋白免疫反应的中间神经元数量（推测是 GABA 能抑制性中间神经元的标记）在整个大脑皮层中减少，主要是在 PME 病例中。改变谷氨酸兴奋毒性的谷氨酸转运蛋白的表达相对较少。同样，四例神经元蜡样质脂褐素沉着症（NCL）的尸检显示，大脑皮层中钙结合蛋白的表达减少，而谷氨酸转运蛋白的表达得以保留。关于拉福拉病，我们对三例尸检病例中的神经变性进行了免疫组织化学检查，并使用 ELISA 评估了从两名患者分离的尿液和血清中的氧化产物。在尸检大脑和尿液样本中都发现氧化产物在 DNA 和脂质上的沉积增加。尽管胶质细胞谷氨酸转运蛋白 EAAT1 的表达相对保留，但另一种胶质细胞谷氨酸转运蛋白 EAAT2 的表达在 3 个尸检病例中有所降低，无论是否存在拉福拉小体。这些发现表明，不同的病理机制似乎与引起 PME 的每种疾病的癫痫发生有关。较少的

项目成果

Manual for paramedical staff in epilepsy, No.9(In : Hayashi M, Shihara H, Igarashi K, Hisada N, Shiratori Y.)

癫痫辅助医务人员手册第 9 号（作者：Hayashi M、Shihara H、Igarashi K、Hisada N、Shiratori Y.）

• 发表时间: 2004
• 作者: Hayashi M.

Neuropathological evaluation of the diencepharon, basal ganglia and upper brainstem in alobar holoprosencephaly.

前脑无裂畸形的间脑、基底神经节和上脑干的神经病理学评估。

• 发表时间: 2004
• 期刊: Acta Neuropathologica 107・3
• 作者: Hayashi M;Araki S;Kumada S;Itoh M;Morimatsu Y;Matsuyama H
• 通讯作者: Matsuyama H

Araki S, Hayashi M, Tamagawa K, et al.: "Neuropathological analysis in spinal muscular atrophy type II."Acta Neuropathologica. 106・5. 441-448 (2003)

Araki S、Hayashi M、Tamakawa K 等：“脊髓性肌萎缩症 II 型的神经病理学分析”。Acta Neuropathologica 106・5（2003 年）。

Nine-year-girl presenting familial occurrence of progressive developmental Abnormalities.

九岁女孩出现家族性进行性发育异常。

• 发表时间: 2002
• 期刊: Neuoropathology 22・4
• 作者: Hayashi M

Hamano K, Kumada S, Nagata J, Kurata K, Hayashi M, Kojima H: "Autopsy case of multiple anomalies with hypoplastic cerebrum, eyes, and endocrine organs mimicking Micro syndrome."Journal of Child Neurology. 18・1. 54-57 (2003)

Hamano K、Kumada S、Nagata J、Kurata K、Hayashi M、Kojima H：“大脑、眼睛和内分泌器官发育不良的尸检病例，类似于微综合征”。《儿童神经病学杂志》18・1。 (2003)