Studies on pathogenesis of hypoxic ischemic encephalopathy by using microPET image

microPET图像研究缺氧缺血性脑病发病机制

基本信息

批准号：
17591109
负责人：
SHINTAKU Haruo
金额：
$ 2.24万
依托单位：
Osaka City University
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 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591109/
关键词：
microPET BH4 HIE biopterin neonatal asphyxia hypoxic ischemic encephalopathy NOS NO micro PET

项目摘要

(Introduction) Hypoxic-ischemic encephalopathy (HIE) is induced by intrauterine or perinatal distress and causes neuronal cell loss that presents clinically as either motor dysfunction, stupor, seizure or other neurological sequelae. It is generally accepted that free radicals, including nitric oxide (NO), play an important role in the pathophysiology of ischemic neuronal death. Recently, it has been reported that decreased levels of tetrahydrobiopterin (BH4) may also cause neuronal cell loss in HIE. In this study, we investigated the change in plasma and brain BH4 levels using a newborn piglet hypoxic ischemic (HI) model and evaluated FDG microPET imaging in the brain. (Methods) The animals used in this study were piglets a few days old with a mean weight of 2 kg. The animals were ventilated with a mixture of 6% oxygen and 94% nitrogen, followed by clamping of the bilateral common carotid arteries for 45 minutes. The clamps were then removed and the animals resuscitated with pure oxyg … More en. These HI animals represented the experimental model while sham-treated animals served as controls. Blood samples were obtained at 0, 4, 8 and 12 hours after resuscitation. Plasma biopterin and neopterin levels were determined using high performance liquid chromatography after iodine oxidation in acidic conditions. (Results) In plasma, biopterin concentrations after HI insult increased more at 0 h (377.9 ± 78.7 nM) than before HI insults (80.1 ± 4.3 nM). The values of plasma biopterin peaked at 4 h (604.8 ± 200.9 nM) and slightly decreased at 12 h (445.9 ± 57.8 nM). Plasma neopterin was not detectable in any sample from experimental piglets. However, the biopterin concentration in the cerebral cortex did not increase until 12 hours after HI insults. The brains of the experimental animals on gross examination appeared edematous but no cysts were observed at 12 h. In microPET imaging, HI insult significantly reduced the intense (18)F-FDG uptake by brain tissue after 24 h. (Conclusion) We identified the imbalance of biopterin levels between plasma and brain tissue in the acute phase of HI insult in the cerebral cortex. MicroPET imaging showed low activity in brain tissue after HI. It seemed to enlarge neuronal damage because of the increase in superoxide production due to insufficiency of BH4 production in the brain. Less

（引言）缺氧 - 缺血性脑病（HIE）是由子宫内或围产期障碍诱导的，并引起神经元细胞丧失，该神经元细胞丧失在临床上作为运动功能障碍，昏昏欲睡，癫痫发作或其他神经系统后遗症。人们普遍认为，包括一氧化氮（NO）在内的自由基在缺血性神经元死亡的病理生理中起重要作用。最近，据报道，提高四氢无生物蛋白酶（BH4）的水平也可能导致HIE神经元细胞损失。在这项研究中，我们使用新生儿小猪缺血（HI）模型研究了血浆和脑BH4水平的变化，并评估了大脑中的FDG MicroPET成像。（方法）这项研究中使用的动物是几天大的小猪，平均体重为2 kg。用6％氧和94％氮的混合物对动物进行通风，然后将双侧共同颈动脉夹紧45分钟。然后将夹具除去，并用纯氧气复苏……更多。这些HI动物代表了实验模型，而虚假处理的动物用作对照。复苏后的0、4、8和12小时获得血液样本。在酸性条件下碘氧化后，使用高性能液相色谱法测定血浆生物蛋白和新近翅目水平。（结果）血浆中，HI损伤后的生物蛋白浓度在0 h（377.9±78.7 nm）时增加了HI损伤之前（80.1±4.3 nm）。血浆生物蛋白的值在4 h（604.8±200.9 nm）峰值，在12 h（445.9±57.8 nm）时略有降低。在实验仔猪的任何样品中，都无法检测到血浆新近肽。但是，直到HI侮辱后12小时，大脑皮层中的生物蛋白浓度才增加。实验动物在总检查中的大脑似乎是水肿，但在12小时时未观察到囊肿。在MicroPET成像中，HI损伤显着降低了24小时后脑组织的强烈（18）F-FDG摄取。（结论）我们确定了在脑皮质中HI损伤的急性阶段，血浆和脑组织之间生物蛋白水平的不平衡。 MicroPET成像显示HI后脑组织的活性较低。由于大脑中BH4产生不足，超氧化物产生增加，它似乎会扩大神经元损害。较少的

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Advances in Phenylketonuria and Tetrahydrobiopterin

苯丙酮尿症和四氢生物蝶呤的研究进展

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Satoshi Funaki;Shori Takahashi;Naohiro Wada;Hitohiko Murakami;Kensuke Harada;Shintaku H
通讯作者：
Shintaku H

Biopterin in the acute phase of hypoxia-ischemia in a neonatal pig model

DOI：
10.1016/j.braindev.2007.04.009
发表时间：
2008-01-01
期刊：
BRAIN & DEVELOPMENT
影响因子：
1.7
作者：
Fujioka, Hiroki;Shintaku, Haruo;Yamano, Tsunekazu
通讯作者：
Yamano, Tsunekazu

Prenatal diagnosis of tetrahydrobiopterin deficiency (2006)

四氢生物蝶呤缺乏症的产前诊断（2006）

DOI：
发表时间：
期刊：
PKU ＆ BH4 : Advances in Phenylketonuria and Tetrahydrobiopterin.(Blau N edt.) SPS, Heibronn
影响因子：
0
作者：
Nishida M;Okumura Y;Fujimoto S;Shiraishi I;Itoi T;Hamaoka K.;立花直子監修;Shintaku H
通讯作者：
Shintaku H

PKU ＆ BH4 : Advances in Phenylketonuria and Tetrahydrobiopterin. (Blau N edt.) SPS, Heibronn

PKU 和 BH4：苯丙酮尿症和四氢生物蝶呤的进展（Blau N 编辑）SPS，Heibronn。