Detection of reperfusion injury using PET in a monkey model of cerebral ischemia

Abstract

Several studies of focal ischemia and reperfusion in animal models have proposed that reperfusion contributes to brain damage. However, the extent to which reperfusion affects the brain, especially in acute stroke patients, remains unclear. Our purpose in this study was to determine whether reperfusion injury can be detected with PET and to clarify the extent to which reperfusion contributes to brain damage.

Methods: The right middle cerebral artery (MCA) of cynomolgus monkeys was occluded for 3 h (n = 8) or permanently (n = 5) by a transorbital device. Four consecutive PET studies were performed to assess cerebral blood flow (CBF), oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2).

Results: The extent of necrotic brain damage 8 h after MCA occlusion was significantly (P < 0.05) greater in the transient model than in the permanent model. Cortical damage was greater in the transient model. The MCA occlusion decreased CBF and CMRO2 in deep MCA territory and increased OEF in the cortex. In the permanent model, these changes continued throughout the experiment. In the transient model, the reperfusion induced postischemic hyperperfusion in the cortex, which showed necrotic damage at the end of the experiment. In this area, OEF and CMRO2 were decreased by reperfusion.

Conclusion: The results suggest that reperfusion may strongly contribute to cortical damage. PET studies revealed that reperfusion decreased OEF and CMRO2 in the hyperperfused cortex. These changes may indicate reperfusion injury.