The ovine cerebral venous system: comparative anatomy, visualization, and implications for translational research.

Anke Hoffmann,Holm Schneider,Johannes Boltze,Donald Lobsien,Björn Nitzsche,Johannes Seeger,Michael H Stoffel,Piotr Walczak

doi:10.1371/journal.pone.0092990

Abstract

Cerebrovascular diseases are significant causes of death and disability in humans. Improvements in diagnostic and therapeutic approaches strongly rely on adequate gyrencephalic, large animal models being demanded for translational research. Ovine stroke models may represent a promising approach but are currently limited by insufficient knowledge regarding the venous system of the cerebral angioarchitecture. The present study was intended to provide a comprehensive anatomical analysis of the intracranial venous system in sheep as a reliable basis for the interpretation of experimental results in such ovine models. We used corrosion casts as well as contrast-enhanced magnetic resonance venography to scrutinize blood drainage from the brain. This combined approach yielded detailed and, to some extent, novel findings. In particular, we provide evidence for chordae Willisii and lateral venous lacunae, and report on connections between the dorsal and ventral sinuses in this species. For the first time, we also describe venous confluences in the deep cerebral venous system and an ‘anterior condylar confluent’ as seen in humans. This report provides a detailed reference for the interpretation of venous diagnostic imaging findings in sheep, including an assessment of structure detectability by in vivo (imaging) versus ex vivo (corrosion cast) visualization methods. Moreover, it features a comprehensive interspecies-comparison of the venous cerebral angioarchitecture in man, rodents, canines and sheep as a relevant large animal model species, and describes possible implications for translational cerebrovascular research.

Highlights

Cerebrovascular diseases such as ischemic stroke and cerebral venous thrombosis (CVT) are major causes of mortality and neurological disabilities in adulthood
Little is known about the venous drainage in the sheep important anatomical differences to other species including humans may limit the use of ovine cerebrovascular disease models
Since profound anatomical knowledge is an important prerequisite for translational research, the present study aimed to provide an in-depth analysis of the ovine intracranial venous blood system and its connections to extracranial veins

Summary

Introduction

Cerebrovascular diseases such as ischemic stroke and cerebral venous thrombosis (CVT) are major causes of mortality and neurological disabilities in adulthood. Thrombolysis is the most important and sometimes only therapeutic option for occlusive cerebrovascular diseases. A number of sheep models emerged [8,9] since this species was found highly practicable for translational research. Among such models, experimental middle cerebral artery occlusion has been described [10,11] and, the intracranial ovine arterial angioarchitecture has been studied in detail [12,13]. Little is known about the venous drainage in the sheep important anatomical differences to other species including humans may limit the use of ovine cerebrovascular disease models. Beyond a detailed anatomical description including hitherto unknown structures in sheep and a comprehensive inter-species comparison of the venous vasculature, this study evaluates the applicability and accuracy of clinical imaging techniques to provide a reliable reference for further translational research on cerebrovascular pathologies in this species

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