Permanent middle cerebral artery occlusion in sheep: a novel large animal model of focal cerebral ischemia

• Published in: Journal of cerebral blood flow and metabolism 2008-12, Vol.28 (12), p.1951-1964
• Main Authors: Boltze, Johannes, Förschler, Annette, Nitzsche, Björn, Waldmin, Daniela, Hoffmann, Anke, Boltze, Christiane M, Dreyer, Antje Y, Goldammer, Axel, Reischauer, Anne, Hartig, Wolfgang, Geiger, Kathrin D, Barthel, Henryk, Emmrich, Frank, Gille, Uwe
• Format: Article
• Language: English
• Subjects: Animals; Arterial Occlusive Diseases - complications; Arterial Occlusive Diseases - pathology; Arterial Occlusive Diseases - physiopathology; Behavior, Animal - physiology; Biological and medical sciences; Brain - blood supply; Brain - diagnostic imaging; Brain - pathology; Brain Ischemia - etiology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cerebral Angiography; Disease Models, Animal; Fluorescent Antibody Technique; Immunohistochemistry; Magnetic Resonance Imaging; Male; Medical sciences; Microscopy, Confocal; Microscopy, Fluorescence; Middle Cerebral Artery - diagnostic imaging; Middle Cerebral Artery - pathology; Neurology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Positron-Emission Tomography; Sheep; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2008.89

As effective stroke treatment by thrombolysis is bound to a narrow time window excluding most patients, numerous experimental treatment strategies have been developed to gain new options for stroke treatment. However, all approaches using neuroprotective agents that have been successfully evaluated in rodents have subsequently failed in clinical trials. Existing large animal models are of significant scientific value, but sometimes limited by ethical drawbacks and mostly do not allow for long-term observation. In this study, we are introducing a simple, but reliable stroke model using permanent middle cerebral artery occlusion in sheep. This model allows for control of ischemic lesion size and subsequent neurofunctional impact, and it is monitored by behavioral phenotyping, magnetic resonance imaging, and positron emission tomography. Neuropathologic and (immuno)-histologic investigations showed typical ischemic lesion patterns whereas commercially available antibodies against vascular, neuronal, astroglial, and microglial antigens were feasible for ovine brain specimens. Based on absent mortality in this study and uncomplicated species-appropriate housing, long-term studies can be realized with comparatively low expenditures. This model could be used as an alternative to existing large animal models, especially for longitudinal analyses of the safety and therapeutic impact of novel therapies in the field of translational stroke research.