Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies

Abstract

Introduction: Restoration of blood flow following ischemic stroke can be achieved by means of thrombolysis or mechanical recanalization. However, for some patients, reperfusion may exacerbate the injury initially caused by ischemia, producing a so-called "cerebral reperfusion injury". Multiple pathological processes are involved in this injury, including leukocyte infiltration, platelet and complement activation, postischemic hyperperfusion, and breakdown of the blood-brain barrier.

Methods/results and conclusions: Magnetic resonance imaging (MRI) can provide extensive information on this process of injury, and may have a role in the future in stratifying patients' risk for reperfusion injury following recanalization. Moreover, different MRI modalities can be used to investigate the various mechanisms of reperfusion injury. Antileukocyte antibodies, brain cooling and conditioned blood reperfusion are potential therapeutic strategies for lessening or eliminating reperfusion injury, and interventionalists may play a role in the future in using some of these therapies in combination with thrombolysis or embolectomy. The present review summarizes the mechanisms of reperfusion injury and focuses on the way each of those mechanisms can be evaluated by different MRI modalities. The potential therapeutic strategies are also discussed.

Fig. 1

DWI images of a rat model with 1 hour of MCA occlusion (MCAO) followed by 10 hours of reperfusion. These images show the evolution of ADC at different times: before ischemia (control), at the end of MCAO, and at different time points of reperfusion. Note the transient recovery of ADC during the early phase of reperfusion, followed by secondary deterioration (reproduced with permission from Olah et al. [13])

Fig. 2

Temporal evolution of mean relative ADC in the end-ischemic lesion volume in a rat model with 1 hour of MCA occlusion (MCAO) followed by 10 hours of reperfusion. Although a significant improvement in ADC attends reperfusion, there is a secondary deterioration likely as a consequence of the reperfusion-related injury (reproduced with permission from Olah et al. [13])

Fig. 3

Graph showing percentages of infarct volume in the four ischemic rat groups (stroke, stroke with local infusion of saline at 20°C and 37°C, and stroke with systemic infusion at 20°C). A significantly (P < 0.001) reduced infarct volume was found in ischemic rats that received a local cooling infusion compared with the rats in the other three groups (reproduced with permission from Ding et al. [88])