Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: hemodynamic changes studied by double-tracer autoradiography.
Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: hemodynamic changes studied by double-tracer autoradiography.
复制标题
大鼠颈动脉内给予 1,3-双（2-氯乙基）-1-亚硝基脲后的神经毒性：通过双示踪剂放射自显影研究血流动力学变化。
DOI：
10.1097/00006123-199107000-00004
复制
发表时间：
1991
期刊：
影响因子：
4.8
通讯作者：
Feindel,W
中科院分区：
文献类型：
--
作者：
Nagahiro,S;Yamamoto,YL;Diksic,M;Mitsuka,S;Sugimoto,S;Feindel,W
采用[14C][α]-氨基异丁酸和[18F]氟安替比林双示踪放射自显影法定量观察大鼠颈动脉内给药1,3 -双（2-氯乙基）-1-亚硝基脲（BCNU）后血脑通透性和局部脑血流的变化。48只雌性Wistar大鼠分为四组。对照组（第一组）给予5%葡萄糖1 ml。另外三组大鼠给予三种不同剂量的5%葡萄糖溶解BCNU: II组大鼠给予1 mg， III组给予3 mg， IV组给予10 mg。示踪剂研究在颈动脉内给予BCNU后第1天或第4至12天进行。II组11只大鼠血脑屏障通透性未见改变，III组5只大鼠中有3只（60%）在24小时内纹状体或海马出现短暂性血脑屏障通透性改变。在同一组的9只大鼠中，有8只（89%）在下丘脑观察到晚期血脑屏障通透性改变，伴有或不伴有组织学改变。IV组所有大鼠血脑屏障通透性均发生改变。[18F]氟安替比林检查的25只大鼠中，有5只观察到灌注侧脑局部血流量与未灌注侧脑血流相比有局灶性增加，但未达到显著水平。血脑屏障通透性、组织学检查和[18F]氟脱氧葡萄糖异质分布研究结果表明，下丘脑、杏仁核、内囊、尾状壳核等同侧皮质下结构的神经毒性发生率最高，与人BCNU白质脑病的组织病理损伤密切相关。血脑屏障通透性的变化是评价颈动脉内缓慢给予BCNU后脑毒性早期体征及其病理生理的有用指标。（神经外科29:19-26,1991）
: Changes in blood-brain (BBB) permeability and local cerebral blood flow after intracarotid administration of 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) were examined quantitatively in rats with double-tracer autoradiography using [14C][alpha]-amino-isobutyric acid and [18F] fluoroantipyrine. Forty-eight female Wistar rats were divided into four groups. The control group (Group 1) received 1 ml of 5% dextrose. The other three groups received three different doses of BCNU dissolved in 5% dextrose: Group II rats received 1 mg, Group III 3 mg, and Group IV 10 mg. The tracer study was performed on Day 1 or Days 4 to 12 after intracarotid administration of BCNU. In 11 rats in Group II, there were no changes of BBB permeability, Transient BBB permeability changes were seen in the striatum or hippocampus in 3 of the 5 rats (60%) in Group III within 24 hours. In 8 of 9 rats (89%) in the same group, late BBB permeability changes were observed in the hypothalamus with or without histological changes. BBB permeability changes were seen in all rats of Group IV. Focal increase of local cerebral blood flow on the infused side compared with the non-infused side of the brain was observed, although not at a significant level, in 5 of 25 rats examined with [18F] fluoroantipyrine. The results of BBB permeability and histological examinations and study of heterogenous distribution by [18F] fluorodeoxyglucose indicated that the ipsilateral subcortical structures such as the hypothalamus, amygdala, internal capsule, and caudate putamen have the highest incidence of neurotoxicity, which are closely related to histopathological damage seen in human BCNU leucoencephalopathy. Changes in BBB permeability are useful indicators for evaluating early signs of brain toxicity and its pathophysiology after slow intracarotid administration of BCNU.(Neurosurgery 29: 19-26, 1991)