Repeated unilateral carotid occlusion in Mongolian gerbils: quantitative analysis of cortical neuronal loss

To develop an experimental model which enables quantitative analysis of chronic neuronal loss in the cerebral cortex, repeated ischemic insult was performed using unilateral carotid artery occlusion in Mongolian gerbils. The effect of the time interval between the repeated ischemic insult on the survival rate of the animals and the amount of cortical neuronal loss were examined. The time course of the cortical neuronal damage in repeated ischemic insult was also studied. We repeated the occlusion four times; i.e., one 10-min and three 7-min occlusions (total 31 min of ischemia). The number of animals surviving for 3 weeks after the last ischemic insult was minimum (15.4%) for animals undergoing occlusions at 1-h intervals and maximum (100%) at 24- and 48-h intervals. The number of ischemic neuronal deaths was also dependent upon the time interval, and it was so pronounced as to allow analysis at intervals of 12 hr or 24 hr in the absence of infarction in the cortex. The number of neuronal deaths could not be determined for animals with occlusion at 1-h intervals due to the production of a large infarction, with which the 3-week survival rate was minimum. The temporal profile of cortical neuronal loss in the repeated ischemic insult at 24-h intervals indicated that the number of cortical neurons significantly decreased until 7 days after the start of the ischemic procedure. This model is useful for clarifying the pathophysiology of chronically developing ischemic neuronal death.