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大鼠双侧颈总动脉永久性闭塞后神经元损伤及中枢乙酰胆碱水平降低

Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat.

作者信息

Ni J W, Matsumoto K, Li H B, Murakami Y, Watanabe H

机构信息

Division of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.

出版信息

Brain Res. 1995 Mar 6;673(2):290-6. doi: 10.1016/0006-8993(94)01436-l.

Abstract

The neuronal damages and the changes in central acetylcholine (ACh) and choline (Ch) contents following permanent occlusion of bilateral common carotid arteries (2VO) of rats were investigated 1 and 4 months after the operation. Two types of neuronal damages were observed in the rats with permanent 2VO. The first type was the infarctions observed in the cerebral cortex and striatum. The infarction in the cortex and striatum was observed in 28.6 and 42.9% of the animals examined 1 month after permanent 2VO, respectively. These ratios did not change even when examined 4 months after permanent 2VO, suggesting that this type of neuronal damage is due to acute ischemic attacks. The second type was progressive neuronal damages observed in the hippocampus and white matter: the neuronal loss in the CA1 subfield appeared 4 months but not 1 month after permanent 2VO and the rarefaction of white matter which was observed 1 months after permanent 2VO and markedly increased 4 months after the operation. Moreover, ACh level significantly decreased in the striatum but not in the cortex, hippocampus or hypothalamus 1 month after permanent 2VO, while the ACh levels in the cortex, striatum and hypothalamus, and Ch levels in all the regions tested significantly decreased when tested 4 months after the operation. These changes did not accompany necrosis. These results suggest that the progressive neuronal degeneration and cholinergic dysfunction following the permanent 2VO are in part involved in chronic cerebral hypoperfusion-induced long-lasting cognition deficits in rats.

摘要

在大鼠双侧颈总动脉永久性闭塞(2VO)术后1个月和4个月,研究了神经元损伤以及中枢乙酰胆碱(ACh)和胆碱(Ch)含量的变化。在永久性2VO大鼠中观察到两种类型的神经元损伤。第一种类型是在大脑皮层和纹状体中观察到的梗死。在永久性2VO术后1个月检查的动物中,分别有28.6%和42.9%的动物在皮层和纹状体中观察到梗死。即使在永久性2VO术后4个月检查,这些比例也没有变化,表明这种类型的神经元损伤是由于急性缺血发作所致。第二种类型是在海马体和白质中观察到的进行性神经元损伤:CA1亚区的神经元丢失在永久性2VO术后4个月出现,但1个月时未出现,白质稀疏在永久性2VO术后1个月观察到,并在术后4个月明显增加。此外,在永久性2VO术后1个月,纹状体中的ACh水平显著降低,但在皮层、海马体或下丘脑未降低,而在术后4个月检查时,皮层、纹状体和下丘脑的ACh水平以及所有测试区域的Ch水平均显著降低。这些变化不伴有坏死。这些结果表明,永久性2VO后的进行性神经元变性和胆碱能功能障碍部分参与了大鼠慢性脑灌注不足引起的长期认知缺陷。

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