Ischemia-reperfusion injury in stroke

Abstract

Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. While the ultimate goal of therapy in ischemic stroke is geared towards restoration of blood flow, even when mitigation of initial tissue hypoxia is successful, exacerbation of tissue injury may occur in the form of cell death, or alternatively, hemorrhagic transformation of reperfused tissue. Animal models have extensively demonstrated the concept of reperfusion injury at the molecular and cellular levels, yet no study has quantified this effect in stroke patients. These preclinical models have also demonstrated the success of a wide array of neuroprotective strategies at lessening the deleterious effects of reperfusion injury. Serial multimodal imaging may provide a framework for developing therapies for reperfusion injury.

Keywords: Collaterals; Ischemia-reperfusion injury; MRI; Neuroprotection; Stroke.

Fig. 1

The outcomes of recanalization following vessel occlusion. In a percentage of patients, both recanalization and reperfusion are successful and lead to tissue salvage and recovery. The no-reflow phenomenon occurs when, in spite of successful mechanical recanalization, no flow is restored to the ischemic tissue bed and is thought in part to be a result of downstream vascular resistance. The third scenario, which has been demonstrated widely in animal models of stroke, is the instance where recanalization and reperfusion are both successful. However, the outcome is cell death or hemorrhagic transformation rather than tissue salvage.

Fig. 2

Schematic drawing of method for assessment of reperfusion injury in stroke patients. PWI = Perfusion-weighted images. Perfusion-weighted MRI images are acquired during the acute phase and after revascularization attempts. Reperfusion injury assessed by voxel-based comparison of the reperfused area and then subsequently undergoing irreversible cell death as measured by FLAIR sequence and/or hemorrhage as demonstrated by GRE sequence.

Fig. 3

Demonstration of ischemia-reperfusion injury using serial multimodal MRI. a A 68-year-old woman with untreated atrial fibrillation presenting with aphasia, hemianopsia, right-sided weakness and sensory loss. The patient was treated with intravenous tPA followed by mechanical recanalization with MERCI device (AOL 3, TICI 2a). Serial change in T_max shows improved perfusion; the perfusion deficit (T_max >6 s) changed from 17.9 to 7.1 ml with resultant cell death (FLAIR) in spite of improved perfusion at follow-up day 5. b A 78-year-old woman with untreated paroxysmal atrial fibrillation presenting with left-sided hemiparesis, neglect and dysarthria. The patient was treated with intravenous tPA followed by mechanical recanalization with Penumbra device (AOL 2, TICI 2b). Serial change in T_max shows improved perfusion; the perfusion deficit (T_max >6 s) changed from 16.5 to 3.4 ml with resultant hemorrhagic transformation (GRE) in spite of improved perfusion at follow-up day 5.