Low-dose lipopolysaccharide injection prior to subarachnoid hemorrhage modulates Delayed Deterioration associated with vasospasm in subarachnoid hemorrhage.
Low-dose lipopolysaccharide injection prior to subarachnoid hemorrhage modulates Delayed Deterioration associated with vasospasm in subarachnoid hemorrhage.
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蛛网膜下腔出血前注射低剂量脂多糖可调节与蛛网膜下腔出血血管痉挛相关的延迟恶化。
DOI：
10.1007/978-3-7091-1192-5_45
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Provencio,JJavier
中科院分区：
文献类型：
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作者：
Smithason,Saksith;Moore,ShariK;Provencio,JJavier
越来越多的证据表明，炎症在蛛网膜下腔出血（SAH）后血管痉挛相关迟发性恶化（DDAV）的发展中起作用。脂多糖（LPS）是先天性炎症系统的激活剂，其在动物模型中引起DDAV。低剂量LPS的作用已被证明在中风模型中具有保护作用，但尚未在SAH中进行研究。研究了两种处理：（1）在SAH前24小时注射0.6 mg/kg的单次腹膜内剂量和（2）在SAH前施用四次每日剂量。在第6天通过印度墨水血管造影术确定DDAV;在不同的动物队列中进行行为测试，并通过斑点印迹法完成脑趋化因子水平的分析。与SAH组相比，单次注射ldLPS组（1 ×1）的血管口径有所改善（p< 0.05）。多次注射组（ldLPS ×4）血管管径与SAH相似（p< 0.05）。ldLPS ×1改善了巴恩斯迷宫测试的表现，而ldLPS ×4则较差（p< 0.001）。炎症趋化因子KC（角质细胞衍生趋化因子）的脑水平在ldLPS ×1组中降低，在ldLPS ×4组中升高。单次注射低剂量LPS预处理对血管痉挛相关延迟恶化（DDAV）具有保护作用，而多次注射过程加重了DDAV。这进一步支持炎症在DDAV的发展中起重要作用，并且调节炎症系统可能是SAH未来治疗的潜在靶点。
There is increasing evidence that inflammation plays a role in the development of Delayed Deterioration associated with vasospasm (DDAV) after subarachnoid hemorrhage (SAH). Lipopolysaccharide (LPS) is an activator of the innate inflammatory system that causes DDAV in animal models. The effect of low-dose LPS has been shown to be protective in stroke models but has not been investigated in SAH. Two treatments were studied: (1) a single intraperitoneal dose of 0.6 mg/kg injected 24 h prior to SAH and (2) four daily doses administered prior to SAH. DDAV was determined by India ink angiography at day 6; behavioral testing was done in a different cohort of animals, and analysis of brain chemokine levels was accomplished by dot blot. Vessel caliber was improved compared to the SAH group in the single-injection group (ldLPS ×1) (p< 0.05). In the multiple-injection group (ldLPS ×4), the vessel caliber was similar to SAH (p< 0.05). ldLPS ×1 improved performance on the Barnes maze test, whereas the ldLPS ×4 was worse (p< 0.001). Brain levels of the inflammatory chemokine KC (keratinocyte-derived chemokine) were decreased in the ldLPS ×1 and increased in the ldLPS ×4 group. Single-injection low-dose LPS preconditioning was protective for delayed deterioration associated with vasospasm (DDAV), whereas the multiple-injection course exacerbated DDAV. This further supports that inflammation plays an important role in the development of DDAV, and that modulating the inflammatory system may be a potential target for future therapies in SAH.