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改良的 2VO 缺血方案引起的认知障碍与标准方法诱导的相似,但存活率更高。

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate.

机构信息

Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

出版信息

Braz J Med Biol Res. 2010 Dec;43(12):1178-83. doi: 10.1590/s0100-879x2010007500124. Epub 2010 Nov 12.

Abstract

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(₈,₁₇₂) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(₂,₄₄) = 7.6884, P < 0.001), 3rd (F(₂,₄₄) = 21.481, P < 0.00001) and 4th trials (F(₂,₄₄) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02).

摘要

永久性双侧颈总动脉闭塞(2VO)在大鼠中已被确立为一种有效的实验模型,用于研究慢性脑低灌注对认知功能和神经退行性过程的影响。我们的目的是比较标准 2VO 手术程序(同时进行动脉结扎)和改良方案的认知和形态学结果,改良方案在两次动脉闭塞之间间隔 1 周,以避免脑血流的突然减少,这通过水迷宫中的动物表现和对海马体和纹状体的损伤扩展来评估。3 个月大的雄性 Wistar 大鼠(N=47)接受永久性双侧颈总动脉结扎的慢性低灌注,使用标准或改良方案,右侧颈总动脉首先被结扎。手术 3 个月后,通过水迷宫评估大鼠的表现,以研究对空间学习和记忆的长期影响,并对其大脑进行处理,以估计海马体体积和纹状体面积。两组低灌注大鼠均表现出参考(F(₈,₁₇₂) = 7.0951,P < 0.00001)和工作空间记忆缺陷[2 次(F(₂,₄₄) = 7.6884,P < 0.001),3 次(F(₂,₄₄) = 21.481,P < 0.00001)和 4 次试验(F(₂,₄₄) = 28.620,P < 0.0001)];然而,在研究的脑结构中没有发现组织萎缩的证据。尽管行为和形态学结果相似,但改良方案组的大鼠在实验的 3 个月内存活率显著增加(P < 0.02)。

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