Protective role of fingolimod (FTY720) in rats subjected to subarachnoid hemorrhage.
Protective role of fingolimod (FTY720) in rats subjected to subarachnoid hemorrhage.
复制标题
DOI：
10.1186/s12974-015-0234-7
复制
发表时间：
2015-01-27
影响因子：
9.3
通讯作者：
Testai FD
中科院分区：
文献类型：
--
作者：
Xu HL;Pelligrino DA;Paisansathan C;Testai FD
蛛网膜下腔出血（SAH）是一种神经急症，药物治疗选择有限。炎症越来越被认为是这种情况下脑损伤的关键致病因素。在本研究中，我们检测了免疫调节剂fingolimod对SAH大鼠的神经保护作用。我们采用血管内大鼠SAH穿孔模型。动物分为四组：(1)假载具；(2) sham-fingolimod;(3) SAH-vehicle;(4) SAH-fingolimod。大鼠在假手术或SAH后3小时腹腔注射载药液或fingolimod （0.5 mg/kg）。在48小时内使用封闭的颅窗和活体显微镜系统来评估神经炎症，其表现为罗丹明- 6g标记的心肌小静脉白细胞运输，以及心肌小动脉对各种血管扩张剂的扩张反应，包括高血氧症，局部应用乙酰胆碱，腺苷和s -亚硝基-n -乙酰青氨胺。此外，还评估了运动感觉功能。与假药组大鼠相比，sah药组大鼠心梗静脉腔内白细胞黏附增加4倍。芬戈莫德治疗大大降低了血管内白细胞粘附。经药物处理的SAH动物对所有血管扩张剂的动脉反应均显著降低，在芬戈莫德的存在下，血管反应性在很大程度上得以保留。此外，在sah后48小时获得的神经学评分表明，载具治疗组（与假载具手术对照组相比）存在显著的神经功能缺陷。芬戈莫德部分减少了这些缺陷（与车辆处理的SAH组相比，P < 0.0001）。用芬戈莫德治疗大鼠，可以明显限制血管内白细胞与心梗小静脉的粘附，保留心梗小动脉的扩张功能，并改善SAH大鼠的神经预后。
Subarachnoid hemorrhage (SAH) is a neurological emergency with limited pharmacological treatment options. Inflammation is increasingly recognized as a key pathogenic contributor to brain injury in this condition. In the present study, we examined the neuroprotective effects of the immunomodulatory agent, fingolimod, in rats subjected to SAH. We utilized an endovascular rat perforation model of SAH. Animals were divided into four groups: (1) sham-vehicle; (2) sham-fingolimod; (3) SAH-vehicle; and (4) SAH-fingolimod. Rats received either vehicle solution or fingolimod (0.5 mg/kg) intraperitoneally 3 hours after sham surgery or SAH. A closed cranial window and intravital microscope system was used at 48 hours to assess neuroinflammation, which was represented by rhodamine-6G-labeled leukocyte trafficking in pial venules, and pial arteriolar dilating responses to a variety of vasodilators, including hypercapnia, and topically-applied acetylcholine, adenosine, and S-nitroso-N-acetyl penicillamine. In addition, motor-sensory function was evaluated. Compared to sham-vehicle rats, SAH-vehicle animals displayed a four-times greater increase in pial venular intraluminal leukocyte adhesion. Treatment with fingolimod largely reduced the intravascular leukocyte adhesion. Vehicle-treated SAH animals displayed a significant decrease in pial arteriolar responses to all the vasodilators tested and vascular reactivity was preserved, to a significant degree, in the presence of fingolimod. In addition, neurological scores obtained at 48 hours post-SAH indicated significant neurological deficits in the vehicle-treated group (versus sham-vehicle surgical control). Those deficiencies were partially reduced by fingolimod (P < 0.0001 compared to the vehicle-treated SAH group). Treatment of rats with fingolimod was associated with a marked limitation in the intravascular adhesion of leukocytes to pial venules, preserved pial arteriolar dilating function, and improved neurological outcome in rats subjected to SAH.
登录
查看更多内容
影响因子：
3.7
作者：
Kooijman E;Nijboer CH;van Velthoven CT;Mol W;Dijkhuizen RM;Kesecioglu J;Heijnen CJ
通讯作者：
Heijnen CJ
影响因子：
4.1
作者：
CHYATTE, D;SUNDT, TM
通讯作者：
SUNDT, TM
芬戈莫德治疗脑出血的 2 臂概念验证研究
影响因子：
29
作者：
Fu, Ying;Hao, Junwei;Shi, Fu-Dong
通讯作者：
Shi, Fu-Dong
影响因子：
11
作者：
Fassbender, K;Hodapp, B;Hennerici, M
通讯作者：
Hennerici, M
影响因子：
8.3
作者：
Britz, Gavin W.;Meno, Joseph R.;Ngai, Al C.
通讯作者：
Ngai, Al C.