Wakita Hideaki, Ruetzler Christl, Illoh Kachikwu O, Chen Yong, Takanohashi Asako, Spatz Maria, Hallenbeck John M
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4476, USA.
J Cereb Blood Flow Metab. 2008 Feb;28(2):341-53. doi: 10.1038/sj.jcbfm.9600528. Epub 2007 Jul 18.
Vascular cognitive impairment (VCI) is the second most prevalent type of dementia in the world. The white matter damage that characterizes the common subcortical ischemic form of VCI can be modeled by ligating both common carotid arteries in the Wistar rat to induce protracted cerebral hypoperfusion. In this model, we find that repetitive intranasal administration of recombinant E-selectin to induce mucosal tolerance and to target immunomodulation to activating blood vessels potently suppresses both white matter (and possibly gray matter) damage and markers of vessel activation (tumor necrosis factor and E-selectin); it also preserves behavioral function in T-maze spontaneous alternation, T-maze spatial discrimination memory retention, and object recognition tests. Immunomodulation may be an effective novel strategy to prevent progression of VCI.
血管性认知障碍（VCI）是全球第二常见的痴呆类型。VCI常见的皮质下缺血形式的特征性白质损伤可通过结扎Wistar大鼠的双侧颈总动脉以诱导长期脑灌注不足来模拟。在这个模型中，我们发现重复经鼻给予重组E选择素以诱导黏膜耐受并将免疫调节靶向激活的血管，可有效抑制白质（可能还有灰质）损伤以及血管激活标志物（肿瘤坏死因子和E选择素）；在T迷宫自发交替、T迷宫空间辨别记忆保持和物体识别测试中，它还能保留行为功能。免疫调节可能是预防VCI进展的一种有效的新策略。
