Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage
Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage
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DOI：
10.1161/01.str.0000053848.06436.ab
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发表时间：
2003-02-01
期刊：
影响因子：
8.3
通讯作者：
Niklason, L
中科院分区：
文献类型：
--
作者：
Borel, CO;McKee, A;Niklason, L
背景与目的：在蛛网膜下腔出血（SAH）后的血管痉挛期间，脑血管的结构变化与血管有丝分裂原的作用一致。我们测量了SAH患者脑脊液（CSF）中血小板衍生血管生长因子（PDGFs），并在体内和体外测试了这些因子对脑动脉的影响。方法：对14例SAH患者、6例非SAH患者和8例正常对照进行脑脊液取样。ELISA检测PDGF-AB、转化生长因子- β 1和血管内皮生长因子。采用小鼠模型比较SAH与假手术对照组的脑血管细胞增殖和PDGF染色。将正常人头动脉体外培养7 d，分为人血凝块组和PDGF抗体组和非PDGF抗体组。结果：SAH患者脑脊液中pdgf - ab浓度显著高于非SAH患者和正常对照，无论是在SAH后的第一周，还是在所有测量的时间点。小鼠模型在SAH后观察到平滑肌和成纤维细胞增殖，并在血栓部位观察到这种细胞复制与PDGF蛋白的结合。在人头动脉中，局部血栓刺激血管壁增殖，而增殖被针对PDGFs的中和抗体阻断。结论：SAH患者脑脊液中血管有丝分裂原增加。血管壁细胞的增殖与血管周围血栓有关。细胞增殖和随后的血管壁增厚可能导致迟发性脑血管痉挛综合征。
Background and Purpose-During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro.Methods-CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-beta1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and I without PDGF antibodies.Results-PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs.Conclusions-Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.