BASIC RESEARCH FOR CEREBRAL WHITE MATTER DEMENTIA USING MODELS OF RADIATION-INDUCED DEMENTIA RATS

使用辐射诱发痴呆大鼠模型进行脑白质痴呆的基础研究

• 批准号: 07457307
• 负责人: TAKEUCHI Shigekazu
• 金额: $ 4.86万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457307/
• 关键词: radiation; rat; water maze; passive avordance; apoptosis; GFAP

A course of whole brain irradiation (30Gy (group A) or 25Gy (group B) /single dose, 40Gy/5Gy*8/4weeks (groupC)) was administered to Fischer 344 rats aged just 6 month, while control rats received sham irradiation (group D) to develop a model of radiation-induced learning disability and to examine histologically. A passive avoidance and a Morris water maze task were studied in groups A and C at 6,9 and 12 months postirradiation, and were studied in group B at 12 months postirradiation. Then those rats were examined histologically and immunohistochemically using grial fibrirally acidic protein (GFAP). No learning disabilities nor radiaion necrosis were shown in groups A and C at 6 months after irradiadtion. But GFAP positive astrocytes were slightly increaced in the white matter in group A.At 9 months after irradiadtion, learning disabilities were shown obviously in group A and a little in group C.Many of group A showed radiation necrosis in the fimbria, internal capsule and corpus callo … More sum, while no radiation necrosis were shown in group C.And moderate increase in GFAP positive astrocytes in the white matter were shown in group A.At 12 months after irradiadtion, learning disabilities were shown in groups of A,B and C.The degree of the learning disability were A>B>C.All of group A showed single or multiple radiation necrosis in the fimbria, internal capsule and corpus callosum. And 60% of group B showed radiation necrosis only in the corpus callosum. While no radiation necrosis were shown in group C.And GFAP positive astrocytes were increaced in the white matter (A>B>C) in groups of A,B and C.These phenomena were like so-called that of white matter dementia such as multiple sclerosis or Binswanger syndrome which were recently often reported. In conclusion learning disability can be demonstrated following radiation therapy in rats.We have then irradiated right hemisphere of Fischer 344 neonatal rats and examined subsequent change of apoptosis in the white matter. Fischer 344 rats at the age of 7 days were employed. The right hemisphere was irradiated at a single dose of 5,10 and 15Gy. Apoptosis was examined with in situ apoptosis detection kit (Apop Tag ; Oncor corporation) at 2,3,6hours, 1,3, and 5 days post-irradiation. In the irradiated hemisphere apoptotic cells were found in the subcortical white matter, hippocampal dentate gyrus (HDG) and subependymal layr of the lateral ventricule at 3th after irradiation. Apoptotic cells were increaced in the HDG and periventricular white matter, and appeared in the internal capsule at 6th after irradiation. The numbers of those positive cells were peaked at 12h after in 15Gy irradiation group and 24h after in 5 and 10Gy irradiation group. And no apoptotic cells were observed in any regions at 5d after irradiation. The results suggest that apoptosis is closely related to injury of cerebral white matter caused by the irradiation insult at the acute phase. Less

6月龄Fischer 344大鼠经全脑照射（30 Gy（A组）或25 Gy（B组）/单次，40 Gy/5 Gy × 8/4周（C组）），对照组（D组）接受假照射，建立放射性学习障碍模型并进行组织学检查。A、C组分别于照射后6、9、12个月进行被动回避和Morris水迷宫实验，B组于照射后12个月进行被动回避和Morris水迷宫实验。采用组织学和胶质纤维酸性蛋白（GFAP）免疫组化方法对各组大鼠进行检测。照射后6个月，A、C两组均未出现学习障碍和放射性坏死。照射后9个月，A组白色出现明显的学习障碍，C组大鼠出现轻度学习障碍，A组大鼠海马伞、内囊和胼胝体出现放射性坏死，C组大鼠海马伞、内囊和胼胝体出现放射性坏死。 ...更多信息 照射后12个月，A、B、C三组均出现学习障碍，学习障碍程度A>B>C，A组海马伞、内囊、胼胝体均出现单发或多发性放射性坏死。B组60%仅胼胝体放射性坏死。A、B、C组白色区GFAP阳性星形胶质细胞增多（A>B>C），与近年来报道的多发性硬化、Binswanger综合征等白色痴呆的病理改变相似。本实验采用Fischer 344新生大鼠右半球照射，观察了照射后白色区细胞凋亡的变化。采用7日龄Fischer 344大鼠。右半球分别接受5、10、15 Gy的单次照射。分别于照射后2、3、6小时、1、3、5天用原位凋亡检测试剂盒（ApopTag; Oncor公司）检测细胞凋亡。照射后第3天，照射侧大脑半球皮质下白色质、海马齿状回及侧脑室室管膜下层可见凋亡细胞。照射后第6天，HDG和脑室周围白色物质中凋亡细胞增多，内囊出现凋亡细胞。15 Gy照射组阳性细胞数在照射后12 h达高峰，5、10 Gy照射组在照射后24 h达高峰。照射后5d，各区域均未见凋亡细胞。结果提示，细胞凋亡与急性期放射损伤所致的脑白色物质损伤密切相关。少