de Leeuw F-E, de Kleine M, Frijns C J M, Fijnheer R, van Gijn J, Kappelle L J
Departments of Neurology, University Medical Center Utrecht, C03-236, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Ann N Y Acad Sci. 2002 Nov;977:306-14. doi: 10.1111/j.1749-6632.2002.tb04831.x.
Cerebral MRI scanning frequently shows white matter lesions in elderly people. They are related to cognitive impairment and may result in dementia. Although vascular risk factors are associated with the presence of white matter lesions, the exact pathogenesis remains unclear. Animal studies have indicated involvement of endothelial cells in the pathogenesis of white matter lesions and possibly dementia. We investigated the relation between endothelial cell activation and white matter lesions in individuals with cerebrovascular disease. In 29 patients with an acute stroke (n = 11) or TIAs associated with a symptomatic internal carotid artery stenosis (n = 18), markers of endothelial cell activation such as intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and sP-selectin were measured by means of ELISA. All individuals underwent 1.5-T MRI scanning. White matter lesions were rated for the periventricular and the subcortical region separately. Individuals with severe periventricular white matter lesions had higher levels of sP-selectin (245.5 ng/mL vs. 172.7 ng/mL, p = 0.01) and sVCAM-1 (547.8 ng/mL vs. 454.0 ng/mL, p = 0.04) than those without. This association was only found in individuals with a symptomatic carotid artery stenosis. No such association was found for subcortical white matter lesions. We did not detect any relation between sICAM-1 and sE-selectin and white matter lesions. Endothelial cell activation may play a role in the pathogenesis of white matter lesions, especially in periventricular white matter. Possibly, this activation represents the influence of vascular factors on the cerebral endothelium as a prelude to increasingly severe small vessel disease.
脑部磁共振成像扫描经常显示老年人存在白质病变。它们与认知障碍有关，可能导致痴呆。尽管血管危险因素与白质病变的存在有关，但其确切发病机制仍不清楚。动物研究表明内皮细胞参与了白质病变和可能的痴呆的发病机制。我们研究了脑血管疾病患者内皮细胞活化与白质病变之间的关系。在29例急性卒中患者（n = 11）或与有症状的颈内动脉狭窄相关的短暂性脑缺血发作患者（n = 18）中，通过酶联免疫吸附测定法测量内皮细胞活化标志物，如细胞间黏附分子-1（sICAM-1）、血管细胞黏附分子-1（sVCAM-1）、可溶性E-选择素和可溶性P-选择素。所有个体均接受1.5-T磁共振成像扫描。分别对脑室周围和皮质下区域的白质病变进行评分。脑室周围白质病变严重的个体，其可溶性P-选择素水平（245.5 ng/mL对172.7 ng/mL，p = 0.01）和可溶性血管细胞黏附分子-1水平（547.8 ng/mL对454.0 ng/mL，p = 0.04）高于无病变个体。这种关联仅在有症状的颈动脉狭窄个体中发现。皮质下白质病变未发现此类关联。我们未检测到可溶性细胞间黏附分子-1和可溶性E-选择素与白质病变之间存在任何关系。内皮细胞活化可能在白质病变的发病机制中起作用，尤其是在脑室周围白质中。这种活化可能代表血管因素对脑内皮的影响，是日益严重的小血管疾病的前奏。
