A modified transorbital baboon model of reperfused stroke

Background and Purpose-Although pathophysiological studies of focal cerebra l ischemia in nonhuman primates can provide important information not obtai nable in rodent models, primate experimentation is limited by consideration s of cost, availability, effort, and ethics. A reproducible and quantitativ e model that minimizes the number of animals necessary to detect difference s between treatment groups is therefore crucial. Methods-Eight male baboons (weight, 22+/-2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid ar tery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (AI) proxi mal to the anterior communicating artery. A tightly controlled nitrous oxid e-narcotic anesthetic allowed for intraoperative motor evoked potential con firmation of middle cerebral artery (MCA) territory ischemia. Animals survi ved to 72 hours or 10 days if successfully self-caring. Outcomes were asses sed with a 100-point neurological grading system, and infarct volume was qu antified by planimetric analysis of both MRI and triphenyltetrazolium chlor ide-stained sections. Results-Infarction volumes (on T2-weighted images) were 32+/-7% (mean+/-SEM ) of the ipsilateral hemisphere, and neurological scores averaged 29+/-9. A ll animals demonstrated evidence of hemispheric infarction, with damage evi dent in both cortical and subcortical regions in the MCA vascular territory . Histologically determined infarction volumes differed by <3% and correlat ed with absolute neurological scores (r=0.9, P=0.003). Conclusions-Transorbital temporary occlusion of the entire anterior cerebra l circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential numbe r of animals required to distinguish between 2 treatment regimens. The anat omic distribution of the infarct and associated functional deficits offer c omparability to human hemispheric strokes.