ABSTRACT
BACKGROUND AND PURPOSE: Current nonhuman primate stroke models are limited by either stroke variability or survivability. A new nonhuman primate stroke model was developed by using endovascular trapping techniques to limit collateral vessels with serial MR imaging and neurologic assessments. MATERIALS AND METHODS: Eight adult rhesus monkeys (female, 7-13 years of age) underwent MR imaging and Spetzler neurologic assessment followed by endovascular stroke induction consisting of superselective endovascular placement of surgical silk sutures into the right MCA by using a trapping technique. Two initial subjects were euthanized immediately following postocclusion MR imaging. The subsequent 6 subjects recovered and underwent follow-up MR imaging and Spetzler neurologic assessments at 48 hours, with 4 being followed to 96 hours. Stroke infarct volumes were measured, and the longitudinal Spetzler clinical neurologic scores were assessed. The brain tissues were harvested and prepared with hematoxylin-eosin staining. RESULTS: Focal permanent cerebral ischemia was induced in the targeted right MCA territory in all subjects. The volumes of the ischemic lesions at 6, 48, and 96 hours were 3.18 ± 1.007 mL (standard error of the mean) (n = 8), 6.70 ± 1.666 mL (standard error of the mean) (n = 6), and 7.23 ± 1.371 mL (standard error of the mean) (n = 4). For the survival animals, the immediate postsurgical Spetzler grading score improved from 60.7 at 24 hours to 68.7 at 48 hours. CONCLUSIONS: We report a trapping modification to an established endovascular suture stroke model that yielded reproducible ischemia and clinically quantifiable neurologic deficits with no strokes in nontarget areas. This technique may be useful in evaluating translational stroke and penumbral imaging research in addition to preclinical testing of neuroprotective therapies.
Subject(s)
Disease Models, Animal , Infarction, Middle Cerebral Artery/pathology , Animals , Endovascular Procedures , Female , Macaca mulatta , Magnetic Resonance ImagingABSTRACT
INTRODUCTION: Cerebrovascular disease occupies second place amongst the causes of mortality in the world. Rapidly after onset of an acute ischemic cerebrovascular accident (CVA) there is irreversible formation of an area affected by the ischemic process (necrotic centre) surrounded by a zone in which reduction of blood flow is less marked. Although the neurons of this region, known as the 'ischemic penumbra', are in a state of 'electrical silence', they may recover if effective treatment is started in time. DEVELOPMENT: Treatment of the patient with an acute ischemic CVA should be concentrated in two areas: restoration of blood flow and neuroprotection. In spite of better understanding of the biochemical, genetic and molecular processes which occur during the process of cerebral ischemia, the development of neuroprotector strategies has been largely fruitless. However, restoration of cerebral blood flow is currently possible in a certain group of patients. The fibrinolytic system is formed by an inactive proenzyme, plasminogen, which may be converted to the active form, plasmin, in the presence of specific activators such as tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). CONCLUSIONS: The effect of thrombolytic treatment is due to dissolution of the fibrin present in the occluding thrombus, with subsequent restoration of the blood flow to the ischemic area. Nevertheless the use of thrombolytic agents has dramatically changed the clinical management of patients with acute ischemic cerebrovascular incidents. Their use involves a significant risk of intracerebral bleeding, which together with the narrow therapeutic window, has made this one of the most controversial fields of current neurology.