Nanri M, Miyake H, Murakami Y, Matsumoto K, Watanabe H
Section of Pharmacology Biological Research Lab., Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1998 Oct;18(5):181-8.
We investigated the time courses of histopathological changes in various brain regions following permanent occlusion of the bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus CA1-3 and dentate gyrus areas 1-3 days after the operation. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2), a marker protein of neuronal dendrites. Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after the 2VO operation. A marked increase in GFAP staining of the astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. Eight-arm radial maze performance was tested from 14 days to 60 days after the operation. The 2VO rats showed fewer initial correct responses than sham-operated control rats during a repeated training period. These findings suggested that the loss in dendritic MAP2 immunoreactivity and an increase in astroglial staining and/or rarefaction of the white matter may cause neuronal death, infarction and learning impairment under conditions of chronic hypoperfusion.
我们研究了大鼠双侧颈总动脉永久性闭塞（2VO）后不同脑区组织病理学变化的时间进程。2VO大鼠在术后1 - 3天，白质出现稀疏，大脑皮质、海马CA1 - 3区和齿状回1 - 3区的神经元发生萎缩。皮质和海马区的这些组织学变化伴随着神经元树突标记蛋白微管相关蛋白2（MAP2）免疫反应性的降低。在2VO手术后3 - 7天观察到胶质纤维酸性蛋白（GFAP）的免疫反应性。结扎后30天，发现大脑皮质和海马区星形胶质细胞的GFAP染色显著增加。术后14天至60天测试八臂放射状迷宫表现。在重复训练期间，2VO大鼠的初始正确反应比假手术对照大鼠少。这些发现表明，在慢性低灌注条件下，树突状MAP2免疫反应性的丧失、星形胶质细胞染色增加和/或白质稀疏可能导致神经元死亡、梗死和学习障碍。
