Schmidt-Kastner Rainald, Aguirre-Chen Cristina, Saul Isabel, Yick Linda, Hamasaki Duco, Busto Raul, Ginsberg Myron D
Department of Neurology, Cerebral Vascular Disease Research Center, D4-5, University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USA.
Brain Res. 2005 Aug 2;1052(1):28-39. doi: 10.1016/j.brainres.2005.06.018.
The effects of oligemia (moderate ischemia) on the brain need to be explored because of the potential role of subtle microvascular changes in vascular cognitive impairment and dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult rats has been used to study effects of oligemia (hypoperfusion) using neuropathological and neurochemical analysis as well as behavioral tests. In this study, BCCAO was induced for 1 week, or 2, 4, and 6 months. Sensitive immunohistochemistry with marker proteins was used to study reactions of astrocytes (GFAP, nestin), and lectin binding to study microglial cells during BCCAO. Overt neuronal loss was visualized with NeuN antibodies. Astrocytes reacted to changes in the optic tract at all time points, and strong glial reactions also occurred in the target areas of retinal fibers, indicating damage to the retina and optic nerve. Astrocytes indicated a change in the corpus callosum from early to late time points. Diffuse increases in GFAP labeling occurred in parts of the neocortex after 1 week of BCCAO, in the absence of focal changes of neuronal marker proteins. No significant differences emerged in the cortex at longer time points. Nestin labeling was elevated in the optic tract. Reactions of microglia cells were seen in the cortex after 1 week. Measurements of the basilar artery indicated a considerable hypertrophy, indicative of macrovascular compensation in the chronic occlusion model. These results indicate that chronic BCCAO and, by inference, oligemia have a transient effect on the neocortex and a long-lasting effect on white matter structures.
由于微血管细微变化在血管性认知障碍和痴呆中可能发挥的作用，需要探究脑缺血（中度缺血）的影响。成年大鼠慢性双侧颈总动脉闭塞（BCCAO）已被用于通过神经病理学、神经化学分析以及行为测试来研究缺血（灌注不足）的影响。在本研究中，诱导BCCAO持续1周、2个月、4个月和6个月。使用标记蛋白的敏感免疫组织化学方法来研究星形胶质细胞（GFAP、巢蛋白）的反应，并使用凝集素结合来研究BCCAO期间的小胶质细胞。用NeuN抗体观察明显的神经元丢失。星形胶质细胞在所有时间点都对视神经束的变化有反应，并且在视网膜纤维的靶区域也出现强烈的胶质反应，表明视网膜和视神经受损。星形胶质细胞显示胼胝体从早期到晚期有变化。BCCAO 1周后，新皮质部分区域GFAP标记弥漫性增加，而神经元标记蛋白无局灶性变化。在更长时间点，皮质无显著差异。视神经束中巢蛋白标记升高。1周后在皮质观察到小胶质细胞的反应。基底动脉测量显示有相当程度的肥大，表明慢性闭塞模型中存在大血管代偿。这些结果表明，慢性BCCAO以及由此推断的缺血对新皮质有短暂影响，对白质结构有长期影响。
