Establishment of a reproducible and minimally invasive ischemic stroke model in swine

Carlos Castaño Marc Melià-Sorolla Alexia García-Serran et al. JCI Insight 2023. Apr 24;8(8):e163398. doi: 10.1172/jci.insight.163398. PMID: 36853828

Abstract: The need for advances in the management/treatment options for ischemic stroke patients requires that upcoming preclinical research uses animals with more human-like brain characteristics. The porcine brain is considered appropriate, although the presence of the rete mirabile (RM) prevents direct catheterization of the intracranial arteries to produce focal cerebral ischemia. To develop a reproducible minimally invasive porcine stroke model, a guide catheter and guide wire were introduced through the femoral artery until reaching the left RM. Using the pressure cooker technique, Squid-12 embolization material was deposited to fill, overflow, and occlude the left RM, the left internal carotid artery, and left circle of Willis wing up to the origins of the middle cerebral arteries (MCAs), mimicking the occlusion produced in the filament model in rodents. Longitudinal multimodal cerebral MRI was conducted to assess the brain damage and cerebral blood supply. The technique we describe here occluded up to the origins of the MCAs in 7 of 8 swine, inducing early damage 90 minutes after occlusion that later evolved to a large cerebral infarction and producing no mortality during the intervention. This minimally invasive ischemic stroke model in swine produced reproducible infarcts and shows translational features common to human stroke.

Funding: This academic research was supported by grants from the Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III PI18/01813 and PI21/01925 to AD and TG, INVICTUS PLUS RD16/0019/0020 and RICORS RD21/0006/0024 that was susceptible to be cofinanced by FEDER/FSE funds, and grants from Agency for Management of University and Research Grants (AGAUR) Catalan Research Group (SGR) 2017SGR1520, 2021SGR00925, and 2019PROD00120 susceptible to be cofinanced by FEDER funds. MMS was supported by a PFIS contract of the ISCIII (FI19/00174), and AGS was supported by contracts associated to 2019PROD00120 and PI18/01813. The IGTP is a Research Center of Catalonia of the CERCA Program/government of Catalonia. The group has received funding from “la Caixa” CI15-00009; from the European Institute of Innovation and Technology (EIT) PoC-2016-SPAIN-04, which receives support from the European Union’s Horizon 2020 research and innovation program; and from the Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE) program 3594-18.