Preclinical Large Vessel Occlusion Stroke Model: Capybaras (Hydrochoerus hydrochoeris)

Existing preclinical large vessel occlusion stroke models have multiple limitations. We evaluated the capybara (Hydrochoerus hydrochoeris), the largest living rodent possessing sizable cerebral cortex with gyral complexity and large caliber vessels that share many intracranial vascular attributes as seen in humans, as a potential large vessel occlusion stroke model.

Conventional angiography was performed in an 18-month-old capybara. We (1) investigated the angiographic architecture, (2) evaluated the feasibility of microcatheter navigation and stent-retriever deployment/retraction in the intracranial vessels and the associated arterial histological changes, (3) evaluated the leptomeningeal collateral pattern following transient large vessel occlusion stroke with coil occlusion, and (4) defined the infarct topography.

The diagnostic portion of the conventional angiogram was uneventfully performed. Five passes of a 3 mm stent-retriever were successfully performed in the right middle cerebral artery. Transient coil occlusion of the left carotid terminus/middle cerebral artery was then pursued for 45 minutes followed by coil removal. Finally, 5 passes of a 3 mm stent-retriever were performed at the basilar artery with unchanged final angiography. The animal was euthanized 2.5 hours after extubation. The middle cerebral and basilar arteries were resected and histopathological sampling of their proximal, mid, and distal sections was pursued. In all vessel segments in which stent retriever devices were deployed, denudation and endothelial stripping of the intima (<5% coverage) but preserved internal elastic lamina, media, and adventitia were observed. Subarachnoid hemorrhage was noted at the right Sylvian cistern. Brain histology revealed neuronal nuclear pyknosis in the left frontal cortex, left thalamus, and left hippocampal CA1 regions on hematoxilin and eosin. Luxol fast blue staining showed pallor and less conspicuous gray-white delineation, particularly in the frontal lobe.

We evaluated a novel preclinical model for thrombectomy. Capybara is a promising animal model for neurointervention. Further validation is warranted.