Wakita H, Tomimoto H, Akiguchi I, Kimura J
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Stroke. 1995 Aug;26(8):1415-22. doi: 10.1161/01.str.26.8.1415.
Activation of glial cells and rarefaction of the white matter have been reported in rat brain after bilateral permanent occlusion of the common carotid arteries. Using this model, we investigated the effects of the immunosuppressant cyclosporin A on the activation of glial cells and the white matter rarefaction.
Both common carotid arteries were ligated bilaterally in 40 male Wistar rats. Twenty-two of these rats received an intraperitoneal injection of cyclosporin A, and the remaining 18 received a vehicle-solution injection. Microglia/macrophages were investigated with immunohistochemistry for the major histocompatibility complex class I and II antigens as well as for leukocyte common antigen. Astroglia were examined with glial fibrillary acidic protein as a marker. Activation of glial cells and white matter rarefaction were then investigated from 7 to 30 days after the ligation.
In vehicle-treated animals, there was a persistent and extensive activation of both microglia/macrophages and astroglia in the white matter, including the optic nerve, optic tract, corpus callosum, internal capsule, and traversing fiber bundles of the caudoputamen. In cyclosporin A-treated rats, the number of activated microglia/macrophages was significantly reduced (P < .01) to approximately one fifth of that in vehicle-treated animals. Similarly, rarefaction of the white matter was much less intense in cyclosporin A-treated rats (P < .01).
Cyclosporin A suppressed both glial activation and white matter changes after chronic cerebral hypoperfusion. These results suggest that immunologic reaction may play a role in the pathogenesis of the white matter changes and that the present model may be useful in investigating the pathophysiology of white matter changes induced by chronic cerebral hypoperfusion.
据报道，双侧颈总动脉永久性闭塞后，大鼠脑内会出现胶质细胞活化和白质稀疏。利用该模型，我们研究了免疫抑制剂环孢素A对胶质细胞活化和白质稀疏的影响。
对40只雄性Wistar大鼠双侧结扎颈总动脉。其中22只大鼠腹腔注射环孢素A，其余18只注射溶剂。通过免疫组织化学检测主要组织相容性复合体I类和II类抗原以及白细胞共同抗原，研究小胶质细胞/巨噬细胞。以胶质纤维酸性蛋白为标志物检测星形胶质细胞。然后在结扎后7至30天研究胶质细胞活化和白质稀疏情况。
在溶剂处理的动物中，白质包括视神经、视束、胼胝体、内囊和尾壳核的穿行纤维束中，小胶质细胞/巨噬细胞和星形胶质细胞均持续广泛活化。在环孢素A处理的大鼠中，活化的小胶质细胞/巨噬细胞数量显著减少（P <.01），降至溶剂处理动物的约五分之一。同样，环孢素A处理的大鼠白质稀疏程度也轻得多（P <.01）。
环孢素A可抑制慢性脑灌注不足后的胶质细胞活化和白质变化。这些结果表明，免疫反应可能在白质变化的发病机制中起作用，且本模型可能有助于研究慢性脑灌注不足引起的白质变化的病理生理学。
