Synergistic Memory Impairment Through the Interaction of Chronic Cerebral Hypoperfusion and Amlyloid Toxicity in a Rat Model
Synergistic Memory Impairment Through the Interaction of Chronic Cerebral Hypoperfusion and Amlyloid Toxicity in a Rat Model
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DOI：
10.1161/strokeaha.111.620179
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发表时间：
2011-09-01
期刊：
影响因子：
8.3
通讯作者：
Kim, Hahn Young
中科院分区：
文献类型：
--
作者：
Choi, Bo-Ryoung;Lee, Sang Rim;Kim, Hahn Young
背景和目的——血管病理学和阿尔茨海默病（AD）病理学已被证明在痴呆症患者的大脑中共存。我们研究了慢性脑灌注不足和β-淀粉样蛋白(Aβ)毒性的相互作用如何在大鼠复合损伤模型中加剧认知障碍。方法-在Wistar大鼠中，通过双侧颈总动脉(BCCAo)永久闭塞来模拟慢性脑灌注不足。此外，使用非生理性 A β 肽（A β 25 至 35）通过双侧脑室内 A β（A β 毒性）模拟 AD 病理学。实验动物分为4组，包括假手术组、单一损伤组（Aβ毒性或BCCAo）和复合损伤组（BCCAo-Aβ毒性）（每组n=7）。使用小动物正电子发射断层扫描测量脑血流量和代谢。进行了 Morris 水迷宫任务、新物体定位和识别测试以及组织学研究，包括神经元细胞死亡、凋亡、神经炎症和 AD 相关病理学。 结果-与 BCCAo 或 A β 毒性组相比，BCCAo-A β 毒性组的空间记忆障碍协同加剧（P
Background and Purpose-Vascular pathology and Alzheimer disease (AD) pathology have been shown to coexist in the brains of dementia patients. We investigated how cognitive impairment could be exacerbated in a rat model of combined injury through the interaction of chronic cerebral hypoperfusion and amyloid beta (A beta) toxicity.Methods-In Wistar rats, chronic cerebral hypoperfusion was modeled by permanent occlusion of bilateral common carotid arteries (BCCAo). Further, AD pathology was modeled by bilateral intracerebroventricular A beta (A beta toxicity) using a nonphysiological A beta peptide (A beta 25 to 35). The experimental animals were divided into 4 groups, including sham, single injury (A beta toxicity or BCCAo), and combined injury (BCCAo-A beta toxicity) groups (n=7 per group). Cerebral blood flow and metabolism were measured using small animal positron emission tomography. A Morris water maze task, novel object location and recognition tests, and histological investigation, including neuronal cell death, apoptosis, neuroinflammation, and AD-related pathology, were performed.Results-Spatial memory impairment was synergistically exacerbated in the BCCAo-A beta toxicity group as compared to the BCCAo or A beta toxicity groups (P