Transition from ischemic neuronal necrosis to infarction in repeated ischemia.

To study morphological changes in the cortex that follow repeated ischemia, one, two, and three 7-min unilateral occlusions of the carotid artery at 6-h intervals, and three, four, and five 7-min similar occlusions at 12-h intervals were produced in gerbils. Animals with one and two 7-min occlusions at 6-h intervals showed selective neuronal necrosis in the cortex; those with three 7-min occlusions at 6-h intervals showed focal infarction in the third layer of the cortex. Animals with three 7-min occlusions at 12-h intervals showed selective neuronal necrosis; those with four 7-min occlusions at 12-h intervals showed focal infarction in the third layer. In animals with five 7-min occlusions at 12 h intervals, infarction affecting all layers of the cortex was seen. Results of the present study indicate that cortical infarction occurred when a brief ischemic insult that does not cause any visible morphological damage in cortical neurons was inflicted repeatedly, and that development of infarction in the cortex following repeated episodes of ischemia depended on both the number of insults and the time intervals between them. This finding suggests that there is a threshold of infarction in repeated ischemia. In our model, various stages of ischemic brain injury could be achieved more easily than in transient ischemia by altering the number of insults or the intervals between them. This model is suitable for studying the pathophysiology on transition from ischemic neuronal necrosis to infarction.