Endothelin-1 in subarachnoid hemorrhage - An acute-phase reactant produced by cerebrospinal fluid leukocytes

被引:137
作者
Fassbender, K
Hodapp, B
Rossol, S
Bertsch, T
Schmeck, J
Schütt, S
Fritzinger, M
Horn, P
Vajkoczy, P
Wendel-Wellner, M
Ragoschke, A
Kuehl, S
Brunner, J
Schürer, L
Schmiedeck, P
Hennerici, M
机构
[1] Heidelberg Univ, Dept Neurol, Clin Mannheim, D-68135 Mannheim, Germany
[2] Heidelberg Univ, Dept Internal Med, Clin Mannheim, D-68135 Mannheim, Germany
[3] Heidelberg Univ, Dept Clin Chem, Clin Mannheim, D-68135 Mannheim, Germany
[4] Heidelberg Univ, Dept Anesthesiol, Clin Mannheim, D-68135 Mannheim, Germany
[5] Heidelberg Univ, Dept Neurosurg, Clin Mannheim, D-68135 Mannheim, Germany
关键词
cerebral ischemia; cytokines; endothelins; subarachnoid hemorrhage; vasospasm;
D O I
10.1161/01.STR.31.12.2971
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:2971 / 2975
页数:5
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