Tomimoto H, Akiguchi I, Suenaga T, Nishimura M, Wakita H, Nakamura S, Kimura J
Department of Neurology, Kyoto University, Faculty of Medicine, Japan.
Stroke. 1996 Nov;27(11):2069-74. doi: 10.1161/01.str.27.11.2069.
The underlying cause of white-matter lesions, which are frequent findings in cerebrovascular disease (CVD) and Alzheimer's disease (AD), remains uncertain. We performed immunohistochemical analysis of serum protein extravasation to investigate the function of the blood-brain barrier in white-matter lesions.
White-matter lesions were estimated by use of Kluver-Barrera staining in patients diagnosed clinicopathologically as having ischemic CVD (n = 14) and AD (n = 12) and from nonneurological control subjects (n = 6). Axonal damages were investigated by use of immunohistochemistry for amyloid protein precursor. Alteration of the blood-brain barrier was examined with fibrinogen and immunoglobulins used as markers. The numbers of HLA-DR-positive microglia and glial fibrillary acidic protein-positive astroglia were examined comparatively.
White-matter lesions were graded as normal (grade 0) in 14 of the 32 cases (44%), slight (grade I) in 10 cases (31%), moderate (grade II) in 6 cases (19%), and severe (grade III) in 2 cases (6%). Amyloid precursor protein was accumulated most frequently in grade II white-matter lesions. Immunohistochemistry for serum proteins labeled astroglial cell bodies and their processes, which seemed to have sequestered extravasated proteins. The groups with detectable white-matter lesions had significantly higher grading scores for fibrinogen and immunoglobulins than the control group (P < .05). Although the higher scores for serum protein extravasation were statistically significant in ischemic CVD cases (P < .05), there was no significant increase in AD cases. Activated microglia and astroglia were more numerous in the groups with white-matter lesions in both ischemic CVD and AD cases, although this increase in the number of astroglia was not evident in regions with clasmatodendrosis.
Dysfunction of the blood-brain barrier is more prominent in white-matter lesions seen in ischemic CVD than in AD and may have a role in the pathogenesis of cerebrovascular white-matter lesions.
白质病变是脑血管疾病（CVD）和阿尔茨海默病（AD）中常见的表现，但其潜在病因仍不明确。我们进行了血清蛋白外渗的免疫组织化学分析，以研究血脑屏障在白质病变中的功能。
通过Kluver-Barrera染色评估临床病理诊断为缺血性CVD（n = 14）、AD（n = 12）患者以及非神经科对照受试者（n = 6）的白质病变情况。采用淀粉样蛋白前体免疫组织化学方法研究轴突损伤。以纤维蛋白原和免疫球蛋白作为标志物检测血脑屏障的改变。比较HLA-DR阳性小胶质细胞和胶质纤维酸性蛋白阳性星形胶质细胞的数量。
32例中14例（44%）白质病变分级为正常（0级），10例（31%）为轻度（I级），6例（19%）为中度（II级），2例（6%）为重度（III级）。淀粉样前体蛋白在II级白质病变中积聚最为频繁。血清蛋白免疫组织化学标记星形胶质细胞体及其突起，这些结构似乎隔离了外渗的蛋白。白质病变可检测组的纤维蛋白原和免疫球蛋白分级评分显著高于对照组（P < 0.05）。虽然血清蛋白外渗较高评分在缺血性CVD病例中有统计学意义（P < 0.05），但在AD病例中无显著增加。在缺血性CVD和AD病例中，白质病变组活化的小胶质细胞和星形胶质细胞数量更多，尽管在轴突断裂区域星形胶质细胞数量的增加不明显。
血脑屏障功能障碍在缺血性CVD的白质病变中比在AD中更突出，可能在脑血管白质病变的发病机制中起作用。
