Endothelin-1 in subarachnoid hemorrhage - An acute-phase reactant produced by cerebrospinal fluid leukocytes
Endothelin-1 in subarachnoid hemorrhage - An acute-phase reactant produced by cerebrospinal fluid leukocytes
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DOI：
10.1161/01.str.31.12.2971
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发表时间：
2000-12-01
期刊：
影响因子：
8.3
通讯作者：
Hennerici, M
中科院分区：
文献类型：
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作者：
Fassbender, K;Hodapp, B;Hennerici, M
背景和目的：内皮素-1是目前已知的最有效的血管收缩剂，目前被认为是介导蛛网膜下腔出血（SAH）时的脑血管痉挛，其可引起迟发性脑缺血。在我们的研究中，我们进行了临床和体外实验来研究SAH中内皮素-1分泌的起源和机制。在SAH患者和对照受试者的脑脊液（CSF）中比较定量白细胞介素[IL]-1 β、IL-6和肿瘤坏死因子-β，浓度与临床特征相关。此外，从SAH患者和对照受试者的CSF中分离的单核白细胞分析了它们的内皮素-1和炎性细胞因子的mRNA表达。最后，在体外实验进行了补充，以调查是否血液和脑脊液共孵育可以触发白细胞的mRNA表达和释放这些factors.Results-Activated单核白细胞在蛛网膜下腔出血患者的脑脊液中合成和释放内皮素-l与已知的急性期反应物（IL-1 β，IL-6，和肿瘤坏死因子-CT）平行。补充的体外实验不仅进一步证实了内皮素-l的白细胞起源，而且还表明，老化和随后的血液溶血足以诱导这样的内皮素-l production. Conclusions，表明内皮素-l是由激活的CSF单核白细胞产生的，表明蛛网膜下腔炎症可能代表一个治疗目标，以防止血管痉挛和迟发性脑缺血后SAH。
Background and Purpose-The most potent vasoconstrictor known, endothelin-l, is currently considered to mediate cerebral vasospasm in subarachnoid hemorrhage (SAH), which can cause delayed cerebral ischemia In our study, we performed clinical and in vitro experiments to investigate the origin and the mechanisms of the secretion of endothelin-l in SAH.Methods-Endothelin-1 and markers of inflammatory host response (interleukin [IL]-1 beta, IL-6, and tumor necrosis factor-cli) were comparatively quantified in the cerebrospinal fluid (CSF) of SAH patients and control subjects, and concentrations were related to clinical characteristics. Furthermore, mononuclear leukocytes isolated from the CSF of SAH patients and control subjects were analyzed regarding their mRNA expression of endothelin-l and inflammatory cytokines. Finally, complementary in vitro experiments were performed to investigate whether coincubation of blood and CSF can trigger leukocytic mRNA expression and release of these factors.Results-Activated mononuclear leukocytes in the CSF of SAH patients synthesize and release endothelin-l in parallel with known acute-phase reactants (IL-1 beta, IL-6, and tumor necrosis factor-ct). Complementary in vitro experiments not only further confirmed this leukocytic origin of endothelin-l but also showed that aging and subsequent hemolysis of blood is sufficient to induce such endothelin-l production.Conclusions-The demonstration that endothelin-l is produced by activated CSF mononuclear leukocytes suggests that subarachnoid inflammation may represent a therapeutic target to prevent vasospasm and delayed cerebral ischemia after SAH.