Relevance of Porcine Stroke Models to Bridge the Gap from Pre-Clinical Findings to Clinical Implementation

Abstract

In the search of animal stroke models providing translational advantages for biomedical research, pigs are large mammals with interesting brain characteristics and wide social acceptance. Compared to rodents, pigs have human-like highly gyrencephalic brains. In addition, increasingly through phylogeny, animals have more sophisticated white matter connectivity; thus, ratios of white-to-gray matter in humans and pigs are higher than in rodents. Swine models provide the opportunity to study the effect of stroke with emphasis on white matter damage and neuroanatomical changes in connectivity, and their pathophysiological correlate. In addition, the subarachnoid space surrounding the swine brain resembles that of humans. This allows the accumulation of blood and clots in subarachnoid hemorrhage models mimicking the clinical condition. The clot accumulation has been reported to mediate pathological mechanisms known to contribute to infarct progression and final damage in stroke patients. Importantly, swine allows trustworthy tracking of brain damage evolution using the same non-invasive multimodal imaging sequences used in the clinical practice. Moreover, several models of comorbidities and pathologies usually found in stroke patients have recently been established in swine. We review here ischemic and hemorrhagic stroke models reported so far in pigs. The advantages and limitations of each model are also discussed.

Autologous Genetically Enriched Leucoconcentrate in the Preventive and Acute Phases of Stroke Treatment in a Mini-Pig Model

“…Therefore, the MCA is the main target of in vivo stroke models [ 16 ]. The peculiarities of the cerebral vascular anatomy of pigs, such as the presence of two to four MCAs on each side of the brain and the involvement of the anterior and posterior cerebral arteries in the circulation in the circle of Willis, present certain difficulties in reaching a reproducible ischemic cerebral infarction [ 14 ]. In the study, we employed the protocol which includes the sequential occlusion of the right common carotid artery and the left MCA.…”

“…Many of the studies testing the new approaches to stroke treatment have been performed on rodent models, which have limited translational potential. The pathophysiology and pathomorphology of stroke in rodents with lissencephalic brains are not fully comparable with brain injuries in human stroke [ 14 ]. Therefore, preclinical stroke studies need to be performed on large mammals that have neuroanatomical, physiological and biochemical characteristics that are close to those of a human.…”

“…Therefore, preclinical stroke studies need to be performed on large mammals that have neuroanatomical, physiological and biochemical characteristics that are close to those of a human. Pigs not only have a gyrencephalic brain and white matter volume similar to that of humans [ 14 ], but they are also genetically closer to humans than mice [ 15 ], which suggests the practicality of using a porcine model of ischaemic stroke for the discovery of new approaches to stroke treatment. Thus, swine stroke models are considered to have translational advantages compared to rodents, dogs, and non-human primates.…”

Model of small-focal ischemic cerebral infarction as a basis for the development of new methods of stroke therapy

“…Существенно бо ́льшая часть экспериментальных научных работ, направленных на разработку методов терапии инсульта, выполнена на грызунах, но результаты, полученные в этих исследованиях, не в полной мере можно экстраполировать на человека [5,6]. Данные, полученные на мелких лабораторных животных, имеют ограниченный трансляционный потенциал для практической медицины, поскольку патологические проявления, возникающие при инсульте у грызунов с лиссэнцефальным мозгом, не сопоставимы с таковыми после инсульта у человека [7].…”

Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix

“…There are various technical issues to overcome to realize a translational success in this field, although there are promising results in animal models [122]. In particular, experimental data are based on rodent models of stroke and are limited to brain tissue (with higher gray/white matter ratio than humans) and could be reconsidered to favor nervous tissue richer in white matter, although this has other limitations [123,124].…”