Uhlig Phillip, Bruckner Peter, Dittrich Ralf, Ringelstein E Bernd, Kuhlenbäumer Gregor, Hansen Uwe
Institut für Physiologische Chemie und Pathobiochemie, Universitätsklinikum Münster, 48129, Münster, Germany.
J Neurol. 2008 Mar;255(3):340-6. doi: 10.1007/s00415-008-0585-4. Epub 2008 Mar 14.
Spontaneous cervical artery dissection (sCAD) is a common cause of stroke in patients below 55 years of age. Hereditary connective tissue disorders, including Ehlers-Danlos syndrome type IV, have been associated with sCAD and suprastructural abnormalities of both collagen fibrils and elastic fibers have been found by transmission electron microscopy in the dermis of about 50% of sCAD patients. Here, we investigated dermal connective tissue abnormalities using a novel method. Transmission and immunogold electron microscopy were used to study mechanically generated fragments of dermal matrix suprastructures, in particular collagen fibrils. Analysis of dermal tissue of sCAD patients revealed structurally abnormal collagen fibrils with irregularly contoured surfaces and increased diameters, often associated with a faint or absent banding pattern. Interestingly, only a small number of fibrils displayed short abnormal sections along the length of the fibril. Collagens I and III were present in normal as well as abnormal sections of the fibrils.However, immunogold labeling for the two proteins was strongly increased in abnormal sections.A systematic blinded investigation of skin biopsies of 31 sCAD patients and 17 controls revealed abnormal collagen fibrils in 7 sCAD patients but none of the controls. We conclude that approximately 20% of sCAD patients show collagen fibril alterations, establishing a promising basis for further investigation of connective tissue aberrations in skin biopsies of sCAD patients.
自发性颈内动脉夹层（sCAD）是55岁以下患者中风的常见原因。遗传性结缔组织疾病，包括IV型埃勒斯-当洛综合征，与sCAD有关，并且在约50%的sCAD患者的真皮中通过透射电子显微镜发现了胶原纤维和弹性纤维的超微结构异常。在此，我们使用一种新方法研究了真皮结缔组织异常。透射电子显微镜和免疫金电子显微镜被用于研究机械产生的真皮基质超微结构片段，特别是胶原纤维。对sCAD患者的真皮组织分析显示，胶原纤维结构异常，表面轮廓不规则且直径增加，常伴有微弱或无条纹图案。有趣的是，只有少数纤维在纤维长度上显示出短的异常节段。I型和III型胶原存在于纤维的正常和异常节段中。然而，这两种蛋白质的免疫金标记在异常节段中强烈增加。对31例sCAD患者和17例对照者的皮肤活检进行系统的盲法研究发现，7例sCAD患者存在胶原纤维异常，而对照者均无。我们得出结论，约20%的sCAD患者表现出胶原纤维改变，为进一步研究sCAD患者皮肤活检中的结缔组织异常奠定了有前景的基础。
