A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Abstract

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood–brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: “symptomatic salvaged tissue” (SST) and “asymptomatic infarcted tissue” (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia–reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.