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Establishment of a reproducible and minimally invasive ischemic stroke model in swine
Carlos Castaño, Marc Melià-Sorolla, Alexia García-Serran, Núria DeGregorio-Rocasolano, Maria Rosa García-Sort, María Hernandez-Pérez, Adrián Valls-Carbó, Osvaldo Pino, Jordi Grífols, Alba Iruela-Sánchez, Alicia Palomar-García, Josep Puig, Octavi Martí-Sistac, Antoni Dávalos, Teresa Gasull
Carlos Castaño, Marc Melià-Sorolla, Alexia García-Serran, Núria DeGregorio-Rocasolano, Maria Rosa García-Sort, María Hernandez-Pérez, Adrián Valls-Carbó, Osvaldo Pino, Jordi Grífols, Alba Iruela-Sánchez, Alicia Palomar-García, Josep Puig, Octavi Martí-Sistac, Antoni Dávalos, Teresa Gasull
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Resource and Technical Advance Neuroscience

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

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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.

Authors

Carlos Castaño, Marc Melià-Sorolla, Alexia García-Serran, Núria DeGregorio-Rocasolano, Maria Rosa García-Sort, María Hernandez-Pérez, Adrián Valls-Carbó, Osvaldo Pino, Jordi Grífols, Alba Iruela-Sánchez, Alicia Palomar-García, Josep Puig, Octavi Martí-Sistac, Antoni Dávalos, Teresa Gasull

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Figure 4

Ex vivo occlusion and brain infarct characterization, with infarct volume correlation to survival and infarct growth.

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Ex vivo occlusion and brain infarct characterization, with infarct volum...
(A) Ventral view of a swine brain, excised shortly after euthanasia, to assess the arterial filling with the black-colored LEA. The region of interest is zoomed in to show the main arteries in different colors. (B) TTC-stained coronal brain slices showing viable (in red) and infarcted (white) gray matter areas. The bottom right drawing shows the silhouette of cryopreserved section 9; slice fragment stained with cresyl violet shows the pale-stained infarct area (yellow line) that roughly matches the infarct in TTC sections 8 and 10. (C and D) Significant Pearson’s correlations (n = 7) between infarct volume and swine survival (C) and infarct volume (D) as measured by TTC or MRI. (E) Growth of infarct volume, corrected by edema, between 90 minutes and 1 day after MCAO (n = 5). C and D include data available for the pig with unsuccessful occlusion; these data are of interest for correlation purposes. MCAO, middle cerebral artery occlusion. ACA, anterior cerebral artery; ICA, internal carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; PCoA, posterior communicating artery. *P = 0.05 versus 90 minutes (paired t test).

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ISSN 2379-3708

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