A modified four vessel occlusion model of global cerebral ischemia in rats.

Background: To develop and evaluate a modified four vessel occlusion (4VO) model of global cerebral ischemia-reperfusion (GCI/R) in rats based on the Pulsinelli and Brierley's method.

New Methods: Vertebral arteries (VAs) were isolated and then permanently ligated with 5-0 nylon surgical sutures under visual conditions. A total of 24 h later, GCI was induced by transient clipping of the bilateral common carotid artery for 20 min. Cognitive function and visual perception were then evaluated by behavioral and histopathological approaches.

Results: There was no significant difference in the survival rates between the groups. The modified 4VO group had a significantly lower body weight at each time point assessed. In the Y-maze test, the percentage of time spent and distance traveled in the III arm was significantly decreased on day 28, suggesting that cognitive function may have been impaired by the modified 4VO model. The modified 4VO procedure induced severe hippocampal damage but did not result in noticeable changes in visual perception, as indicated by the light-dark box test, and analysis of the optic tract and retinal structures. The modified 4VO procedure-induced cognitive deficits were thus likely the result of hippocampal damage, not visual perception.

Comparison With Existing Methods: The advantage of this model is the permanent ligation of the bilateral VAs under visual conditions rather than electrocoagulation, which is performed blind.

Conclusions: This modified 4VO model can mimic the GCI/R method of the Pulsinelli and Brierley and may serve as a valuable tool for studies on GCI/R.