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Open Access Acute Neuronal Injury and Blood Genomic Profiles in a Nonhuman Primate Model for Ischemic Stroke

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Abstract:

The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques. Within hours after middle cerebral artery occlusion (MCAO), infarction was detectable by using diffusion-weighted MRI imaging. The infarcts expanded by 24 h after MCAO and then were detectable on T2-weighted images. The infarcts seen by MRI were consistent with neuronal injury demonstrated histologically. Neurobehavioral function after MCAO was determined by using 2 neurologic testing scales. Neurologic assessments indicated that impairment after ischemia was limited to motor function in the contralateral arm; other neurologic and behavioral parameters were largely unaffected. We also used microarrays to examine gene expression profiles in peripheral blood mononuclear cells after MCAO-induced ischemia. Several genes were altered in a time-dependent manner after MCAO, suggesting that this ischemia model may be suitable for identifying blood biomarkers associated with the presence and severity of ischemia. This NHP stroke model likely will facilitate the elucidation of mechanisms associated with acute neuronal injury after ischemia. In addition, the ability to identify candidate blood biomarkers in NHP after ischemia may prompt the development of new strategies for the diagnosis and treatment of ischemic stroke in humans.

Document Type: Research Article

Affiliations: 1: Department of Neurosurgery, Caribbean Primate Research Center, Animal Resources Center, University of Puerto Rico Medical Sciences, San Juan, Puerto Rico 2: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Department of Biology, Morehouse College, Emory University, Atlanta, Georgia, USA 3: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Emory University, Atlanta, Georgia, USA 4: Unit of Comparative Medicine, Caribbean Primate Research Center, Animal Resources Center, University of Puerto Rico Medical Sciences, San Juan, Puerto Rico 5: Department of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamon, Puerto Rico 6: Department of Radiology, Caribbean Primate Research Center, Animal Resources Center, University of Puerto Rico Medical Sciences, San Juan, Puerto Rico 7: Department of Anesthesiology, Caribbean Primate Research Center, Animal Resources Center, University of Puerto Rico Medical Sciences, San Juan, Puerto Rico 8: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Emory University, Atlanta, Georgia, USA; Department of Physiology, Emory University, Atlanta, Georgia, USA 9: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Emory University, Atlanta, Georgia, USA; Unit of Comparative Medicine, Caribbean Primate Research Center, Animal Resources Center, University of Puerto Rico Medical Sciences, San Juan, Puerto Rico. bford@msm.edu

Publication date: October 1, 2012

More about this publication?
  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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