Purpose To develop a preclinical model of stroke with a large vessel occlusion treated with mechanical thrombectomy.
Materials and methods An ischemic stroke model was created in dogs by the introduction of an autologous clot into the middle cerebral artery (MCA). A microcatheter was navigated to the clot and a stent retriever thrombectomy was performed with the goal to achieve Thrombolysis in Cerebral Ischemia (TICI) 2b/3 reperfusion. Perfusion and diffusion MRI was acquired after clot placement and following thrombectomy to monitor the progression of restricted diffusion as well as changes in ischemia as a result of mechanical thrombectomy. Post-mortem histology was done to confirm MCA territory infarct volume.
Results Initial MCA occlusion with TICI 0 flow was documented in all six hound-cross dogs entered into the study. TICI 2b/3 revascularization was achieved with one thrombectomy pass in four of six animals (67%). Intra-procedural events including clot autolysis leading to spontaneous revascularization (n=1) and unresolved vasospasm (n=1) accounted for thrombectomy failure. In one case, iatrogenic trauma during microcatheter navigation resulted in a direct arteriovenous fistula at the level of the cavernous carotid. Analysis of MRI indicated that a volume of tissue from the initial perfusion deficit was spared with reperfusion following thrombectomy, and there was also a volume of tissue that infarcted between MRI and ultimate recanalization.
Conclusion We describe a large animal stroke model in which mechanical thrombectomy can be performed. This model may facilitate, in a preclinical setting, optimization of complex multimodal stroke treatment paradigms for clinical translation.
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Contributors OWB: designed and performed the experiments, analyzed the data, drafted the manuscript, approved the final manuscript. RMK: performed the imaging experiments, analyzed the data, revised the manuscript, approved the final manuscript. J-YC: performed the experiments, revised the manuscript, approved the final manuscript. EN: critical input for optimization of the model, interpreted the data, revised the manuscript, approved the final manuscript. MM: performed the experiments, interpreted the data, revised the manuscript, approved the final manuscript. JC: performed the experiments, analyzed and interpreted the data, approved the final manuscript. ASP: designed the study, interpreted the data, revised the manuscript, approved the final manuscript. MJG: designed the study, designed and performed the experiments, analyzed and interpreted the data, drafted the manuscript, approved the final manuscript and agrees to be accountable for the accuracy and integrity of the work.
Funding Partially supported by research funding from Rapid Medical. JC was supported by research grants from the Fulbright Program, the Philippe Foundation, and the French Society of Radiology (SFR-CERF). The content is solely the responsibility of the authors and does not reflect the opinions of any sponsors.
Competing interests OWB and RMK declare that they have no competing interests. EN: Fee-for-service consulting for Rapid Medical. MM, J-YC: Fee-for-service consulting for Stryker Neurovascular and InNeuroCo. JC: has received educational scholarships from Medtronic Neurovascular and Microvention/Terumo. ASP: consultant for Medtronic Neurovascular and Stryker Neurovascular; research grants from Medtronic Neurovascular and Stryker Neurovascular. MJG: has been a consultant on a fee-per-hour basis for Cerenovus, Imperative Care, Mivi Neurosciences, Phenox, Route 92 Medical, Stryker Neurovascular; holds stock in Imperative Care and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States–Israel Binational Science Foundation, Anaconda, Cerenovus, Cook Medical, Gentuity, Imperative Care, InNeuroCo, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Neuravi, Neurogami, Philips Healthcare, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, and the Wyss Institute.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data presented in the manuscript.
Presented at This work has been presented in part at the Society of NeuroInterventional Surgery 15th Annual Meeting (SNIS 2018).
Patient consent for publication Not required.