Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats

Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats
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DOI:
10.1016/j.brainres.2005.06.018
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发表时间:
2005-08-02
期刊:
影响因子:
2.9
通讯作者:
Ginsberg, MD
Ginsberg, MD
中科院分区:
医学3区
文献类型:
--
作者:
Schmidt-Kastner, R;Aguirre-Chen, C;Ginsberg, MD

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由于细微的微血管变化在血管性认知障碍和痴呆中具有潜在作用,因此需要探索少血症(中度缺血)对大脑的影响。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和神经化学分析以及行为测试来研究血少(灌注不足)的影响。在这项研究中,BCCAO 被诱导 1 周,或 2、4 和 6 个月。使用标记蛋白进行灵敏的免疫组织化学研究星形胶质细胞(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。使用 NeuN 抗体可观察到明显的神经元损失。星形胶质细胞在所有时间点都会对视束的变化做出反应,视网膜纤维的目标区域也发生强烈的神经胶质反应,表明视网膜和视神经受到损害。星形胶质细胞表明胼胝体从早期到晚期的时间点发生了变化。 BCCAO 治疗 1 周后,在神经元标记蛋白没有局部变化的情况下,新皮质部分区域出现 GFAP 标记的弥漫性增加。在较长的时间点,皮质没有出现显着差异。视束中的巢蛋白标记升高。一星期后在皮质中观察到小胶质细胞的反应。基底动脉的测量表明有相当大的肥大,表明慢性闭塞模型中的大血管代偿。这些结果表明,慢性 BCCAO 以及由此推断的血少对新皮质具有短暂的影响,而对白质结构具有长期的影响。 (c) 2005 Elsevier B.V. 保留所有权利。
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 I 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 I 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 I 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. (c) 2005 Elsevier B.V. All rights reserved.