Intra-Arterial Transplantation of Mitochondria after Ischemic Stroke Reduces Cerebral Infarction

Abstract

Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion. Using murine stroke models of middle cerebral artery occlusion, we demonstrate that it is feasible to deliver viable mitochondria to ischemic brain parenchyma via an intra-arterial route of administration. We also show the beneficial supplemental effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood-brain barrier without hemorrhagic complications. Following delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase neuronal viability. Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.

Keywords: Mitochondria, Ischemic Stroke, Transplantation, Focused Ultrasound, Intra-Arterial