Abstract

BackgroundThe choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are performed in smaller animals, as they are cost-effective and their encephalic vasculature closely models that of humans. Non-human primates are also utilized when confirmation or validation is required on higher levels and to test larger devices. However, working with primates is complex and expensive. Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise. Their cerebrovascular anatomy, however, comes with challenges because of the natural higher external carotid artery perfusion and the existence of a rete mirabile. We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion, limiting external carotid perfusion and dilution.ResultsWe investigated whether unilateral endovascular coil-embolization of external carotid artery branches in swine would lead to increased brain perfusion, altering cerebral circulation so that it more closely models human cerebral circulation. Equal amounts of approximately 4 °C cold saline were injected in 6 Yorkshire pigs into the ipsilateral common carotid artery before and after embolization. Hemispheric temperature changes from pre- and post-embolization were obtained as a measure of brain perfusion and averaged and compared using non-parametric statistical tests (Wilcoxon signed rank test, Mann–Whitney U Test). Graphs were plotted with absolute changes in hemispheric temperature over time to determine peak temperature drop (PTD) and corresponding time to peak (TTP) following the cold bolus injection. There was a 288 ± 90 % increase in ipsilateral brain cooling after embolization indicating improved selective blood flow to the brain due to this vascular modification.ConclusionWe have developed an effective, selective vascular brain model in swine that may be useful as a practical and cost-reducing intermediate step for evaluating target dose–responses for central nervous system drugs and brain selective interventions, such as local hypothermia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1714-7) contains supplementary material, which is available to authorized users.

Highlights

  • The choice of an animal model for cerebrovascular research is often determined by the disease sub‐ type to be studied, as well as the nature of the intervention to be tested

  • Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise for cerebrovascular research [2,3,4,5]. Their pre-encephalic vasculature has been considered problematic because of their pre-cerebral rete that is bilaterally connected to the common carotid artery (CCA) by the ascending pharyngeal artery (AsPharA) [6, 7]

  • We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion while limiting external carotid perfusion and dilution

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Summary

Introduction

The choice of an animal model for cerebrovascular research is often determined by the disease sub‐ type to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise for cerebrovascular research [2,3,4,5] Their pre-encephalic vasculature has been considered problematic because of their pre-cerebral rete that is bilaterally connected to the common carotid artery (CCA) by the ascending pharyngeal artery (AsPharA) [6, 7]. We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion while limiting external carotid perfusion and dilution We believe that this modification will enhance our ability to evaluate brainselective therapeutics and diagnostics, and target doseresponses in this larger non-primate model, a model well-suited for investigating larger endovascular devices and central nervous system drugs

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