Modo M, Sowinski P, Hodges H
Department of Psychology, Institute of Psychiatry, De Crespigny Park, SE5 8AF, London, UK.
Behav Brain Res. 2000 Jun 15;111(1-2):213-21. doi: 10.1016/s0166-4328(00)00160-1.
Hippocampal cell loss was induced by the four-vessel occlusion (4VO) method, a model of global ischaemia. Global ischaemia for 15 min induced a selective damage to the CA1 subfield. Occlusion for 25 min produced a larger cell loss within the CA1 and more variably the CA2, CA3, the striatum and cortex. Ischaemic and sham control groups were assessed on two conditional discrimination tasks (presenting the conditional cues either in the choice arms or the start arm) and two spatial tasks (water maze and a simple spatial discrimination task). No significant effects were found on either of the spatial tasks (apart from the speed measure on the water maze). However, on the conditional discrimination task with the cues in the choice arms, animals with 25 min ischaemia learned the task significantly more slowly than the 15 min ischaemic and control groups. Results for the task with cues presented in the start arm differed according to choice of criterion for learning. With a standard criterion of 90% accuracy on one session controls were significantly superior to both ischaemic groups. However, in this task rats with 15 min occlusion showed the greatest impairment, and were significantly worse than both the controls and the 25 min occlusion group. These results suggest that hippocampal ischaemic damage disrupts the learning of conditional discrimination but not simple spatial tasks. No clear relationship between the extent of hippocampal cell loss and behavioural impairment was evident. These results highlight the critical importance of procedural factors in the assessment of cognitive impairment.
采用四血管闭塞（4VO）法诱导海马细胞损失，该方法是一种全脑缺血模型。全脑缺血15分钟会对CA1亚区造成选择性损伤。缺血25分钟会导致CA1区域内细胞损失更大，CA2、CA3、纹状体和皮质的细胞损失则更具变异性。对缺血组和假手术对照组进行两项条件辨别任务（在选择臂或起始臂呈现条件线索）和两项空间任务（水迷宫和简单空间辨别任务）的评估。在任何一项空间任务中均未发现显著影响（水迷宫中的速度测量除外）。然而，在选择臂中有线索的条件辨别任务中，缺血25分钟的动物学习该任务的速度明显比缺血15分钟的动物和对照组慢。起始臂中有线索的任务结果根据学习标准的选择而有所不同。以一次实验90%的准确率作为标准，对照组明显优于两个缺血组。然而，在这项任务中，缺血15分钟的大鼠表现出最大的损伤，且明显比对照组和缺血25分钟的组差。这些结果表明，海马缺血性损伤会干扰条件辨别学习，但不会影响简单空间任务。海马细胞损失程度与行为损伤之间没有明显的关系。这些结果突出了程序因素在认知损伤评估中的关键重要性。
