Tanaka K, Ogawa N, Asanuma M, Kondo Y, Nomura M
Department of Neuroscience, Okayama University Medical School, Japan.
Brain Res. 1996 Aug 5;729(1):55-65.
The effects of chronic hypoperfusion of cerebral blood flow (CBF) on central cholinergic indices and intellectual functions were investigated in rats. Male Wistar rats, aged 9 weeks, were anesthetized with pentobarbital, and the bilateral common carotid arteries were permanently ligated. Cortical CBF in the hypoperfused rats was markedly decreased at 6 weeks after the operation. In the hypoperfused group, cholinergic indices were changed to consist two phases after the operation, before (acute) and after (chronic) 6 weeks after the operation. At 6 weeks, choline acetyltransferase activity was restored to the sham-operated level compared with the changes in the frontal cortex and thalamus + midbrain at 3 weeks. On the other band, the maximum number of muscarinic acetylcholine receptors was reduced in the frontal cortex, hippocampus and striatum at 6 weeks and thereafter remained at this low level. In discrimination learning task, the percentage of correct responses in the hypoperfused rats was generally reduced in contrast with that of the sham-operated rats, although the number of total responses were not changed. As a consequence, cholinergic dysfunctions correlate with discrimination learning disabilities in the hypoperfused rats. These findings suggest that the hypoperfused rat may be useful for the cerebrovascular type dementia model to clarify pathophysiology.
研究了大鼠脑血流量（CBF）慢性灌注不足对中枢胆碱能指标和智力功能的影响。9周龄雄性Wistar大鼠用戊巴比妥麻醉，双侧颈总动脉永久性结扎。术后6周，灌注不足大鼠的皮质CBF显著降低。在灌注不足组，胆碱能指标在术后出现两个阶段的变化，即术后6周前（急性）和6周后（慢性）。与术后3周额叶皮质和丘脑+中脑的变化相比，术后6周胆碱乙酰转移酶活性恢复到假手术组水平。另一方面，6周时额叶皮质、海马和纹状体中M型乙酰胆碱受体的最大数量减少，此后一直维持在低水平。在辨别学习任务中，与假手术组大鼠相比，灌注不足大鼠的正确反应百分比总体降低，尽管总反应次数没有变化。因此，胆碱能功能障碍与灌注不足大鼠的辨别学习障碍相关。这些发现表明，灌注不足大鼠可能有助于作为脑血管型痴呆模型来阐明病理生理学。
