Neuropathological analysis for the development of new treatment in intractable epilepsy

顽固性癫痫新疗法开发的神经病理学分析

• 批准号: 17591129
• 负责人: HAYASHI Masaharu
• 金额: $ 2.35万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591129/
• 关键词: progressive myoclonus epilepsy; DRPLA; West syndrome; Lennox-Gastaut syndrome; oxidative stress; immunohistochemistry; ELISA; intractable epilepsy; Lennox Gastaut症候群; Hexanoyl lysine; 低血糖発作; Focal cortical dysplasia; 片側巨脳症; 8-Hydroxy-2'-deoxy

Dentatorubral-pallidoluysian atrophy (DRPLA) is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME) in addition to late adult type. We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD) in autopsy cases of DRPLA. Oxidative products to DNA (8-OHdG) were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME. Cytoplasmic immunoreactivity for Cu/ZnSOD was reduced in the external segment of globus pallidus, dentate nucleus and cerebellar cortex in DRPLA cases. Mitochondrial immunoreactivity for MnSOD was reduced in the lenticulate nucleus and cerebellum in DRPLA cases having PME It is likely that oxidative stress can be involved in DRPLA.West syndrome (WS) consists of epileptic spasms, developmental delay, and hypsarrhythmia on EEG. We immunohistochemically examined accumulation of oxidative products and SOD expression in the brains of 4 autopsy cases each with lissencephaly and perinatal hypoxemic ischemic encephalopathy (HIE), and suffering from both WS and Lennox-Gastaut syndrome (LGS). In the absence of destructive changes, 3 of 4 lissencephaly cases and 2 of 4 HIE cases showed neurons immunoreactive for oxidative stress marker to lipids in the midbrain in the WS/LGS autopsy cases. Immunoreactivities for SODs were well preserved in the brain area including the midbrain. We also measured the levels of oxidative stress marker, 8-OHdG and markers for lipid peroxidation such as hexanoyl-lysine adduct (HEL) in the urine and cerebral spinal fluid (CSF) of 11 WS patients using ELISA. In the CSF, 8-OHdG level was increased in 3 of 4 patients in the symptomatic group. HEL level in the CSF was increased in 2 of 7 patients in the cryptogenic group, and in 2 of 4 patients in the symptomatic group. Lipid peroxidation is likely to be involved in the persistence of epileptic seizures in patients with WS.

齿状核红核-苍白球路易氏体萎缩症（DRPLA）除了晚期成人型外，还可分为青少年型和早期成人型，表现为进行性肌阵挛癫痫（PME）。我们用化学方法检测了DRPLA尸检病例中氧化产物的积累和超氧化物歧化酶（SOD）的表达。DNA氧化产物（8-OHdG）主要聚集于延髓核，在DRPLA合并PME的病例中占优势。DRPLA患者苍白球外段、齿状核和小脑皮质的Cu/ZnSOD胞浆免疫反应减弱。结果表明，DRPLA患者PME时小脑和延髓核内MnSOD免疫反应性降低，推测氧化应激可能参与了DRPLA的发病过程。West综合征（WS）表现为癫痫痉挛、发育迟缓和脑电图高度心律失常。我们用化学发光法检测了4例无脑畸形和围产期缺氧缺血性脑病（HIE）尸检病例的脑组织中氧化产物的积累和SOD的表达，并同时患有WS和Lennox-Gastaut综合征（LGS）。在无破坏性改变的情况下，WS/LGS尸检病例中，4例无脑回畸形和4例HIE病例中的3例显示中脑脂质氧化应激标记物免疫反应神经元。SOD的免疫反应性在包括中脑在内的脑区得到了很好的保留。我们还用ELISA法测定了11例WS患者尿液和脑脊液中氧化应激标志物8-OHdG和脂质过氧化标志物己酰赖氨酸加合物（HEL）的水平。在CSF中，症状组4例患者中有3例患者的8-OHdG水平升高。CSF中HEL水平在隐源性组7例患者中的2例中升高，在症状性组4例患者中的2例中升高。脂质过氧化可能参与WS患者癫痫发作的持续性。

项目成果

Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atronhy.

齿状红核-苍白球路易体萎缩神经变性中的氧化应激。

• 发表时间: 2008
• 期刊: J Neurol Sci 264
• 作者: Miyata R;Hayashi M;TanumaN;et. al.
• 通讯作者: et. al.

色素性乾皮症とCockayne症候群の神経病理

着色性干皮病和科凯恩综合征的神经病理学

• 发表时间: 2005
• 期刊: 医学のあゆみ 214・7
• 作者: Hayashi M;Araki S;Kohyama J;et al.;林雅晴
• 通讯作者: 林雅晴

Protracted juvenile neuronal ceroid lipofuscinosis - An autopsy report and immunohistochemical analysis

• DOI: 10.1016/j.braindev.2005.12.004
• 发表时间: 2006-08-01
• 期刊: BRAIN & DEVELOPMENT
• 影响因子: 1.7
• 作者: Anzai, Yuki;Hayashi, Masaharu;Ohya, Tatsuo
• 通讯作者: Ohya, Tatsuo

脳腫瘍が疑われた結節性の形成異常を合併した片側巨脳症の1例

半侧巨脑畸形伴结节性发育不良疑似脑肿瘤一例

• 发表时间: 2007
• 作者: 山本 敦子、由井 嵩子、片桐 朋子、荒木 聡、渡辺 章充、林 雅晴;他
• 通讯作者: 他

脳機能と症候からみる小児神経学

从脑功能和症状看小儿神经病学

• 发表时间: 2007
• 作者: 林雅晴;他
• 通讯作者: 他