A new model of cortical stroke in the rhesus macaque.
Primate models are essential tools for translational research in stroke but are reportedly inconsistent in their ability to produce cortical infarcts of reproducible size. Here, we report a new stroke model using a transorbital, reversible, two-vessel occlusion approach in male rhesus macaques that produces consistent and reproducible cortical infarcts. The right middle cerebral artery (distal to the orbitofrontal branch) and both anterior cerebral arteries were occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery was critical for reducing collateral flow to the ipsilateral cortex. Reversible ischemia was induced for 45, 60, or 90 mins (n=2/timepoint) and infarct volume and neurologic outcome were evaluated. The infarcts were located predominantly in the cortex and increased in size with extended duration of ischemia determined by T(2)-weighted magnetic resonance imaging . Infarct volume measured by 2,3,5-triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic resonance imaging results. Neurologic deficit scores worsened gradually with longer occlusion times. A subset of animals (n=5) underwent 60 mins of ischemia resulting in consistent infarct volumes primarily located to the cortex that correlated well with neurologic deficit scores. This approach offers promise for evaluating therapeutic interventions in stroke.
West
G Alexander
GA
Colorado Brain & Spine Institute, Neurotrauma Research Laboratory, Swedish Medical Center, Englewood, Colorado, USA.
Golshani
Kiarash J
KJ
Doyle
Kristian P
KP
Lessov
Nikola S
NS
Hobbs
Theodore R
TR
Kohama
Steven G
SG
Pike
Martin M
MM
Kroenke
Christopher D
CD
Grafe
Marjorie R
MR
Spector
Maxwell D
MD
Tobar
Eric T
ET
Simon
Roger P
RP
Stenzel-Poore
Mary P
MP
D000818:Animals; D048588:Benzoxazines; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D008253:Macaca mulatta / Q000601:surgery; D008279:Magnetic Resonance Imaging; D008297:Male; D010078:Oxazines
D048588:Benzoxazines; D010078:Oxazines; C028911:cresyl violet