Hyperglycemic Modification to Classical Two-Vessel Occlusion for Inducing Transient Cerebral Ischemia in Sprague-Dawley Rats

Abstract

Cerebral ischemia is widely studied through the employment of experimental animal models. Incomplete global models such as two-vessel occlusion are relevant in the study of disease states which may attenuate cerebral ischemia. Hyperglycemia is known to worsen the consequences of ischemia but has not been exclusively employed. The two-vessel occlusion model, which is unsuccessful when employed in the absence of hypotension and/or hypoxia, is thus ideal for modification to a hyperglycemic model. We therefore describe an established technique for inducing hyperglycemic cerebral ischemia through modification of the two-vessel occlusion model as well as the procedure subsequently used to confirm cerebral injury. This method produces a larger degree of neural injury in males than in females, with estradiol levels negatively correlated to neural injury, confirming trends in research where estrogen is shown to be neuroprotective. Overall, this data is consistent with findings obtained by other groups, showing the neuroprotective nature of endogenous estradiol in rat models, with cyclic female animals sustaining less neural injury than age-matched male and acyclic female counterparts Furthermore, this technique proves to be simple, highly repeatable and cost effective. In conclusion, the hyperglycemic cerebral ischemia model developed as a modification to the two-vessel occlusion model (with exclusion of hypoxia and/or hypotension) proved successful for the study of cerebral ischemia.