Zhiting Zhang1, Shuguo Wang2, Lingli Du3, Ling Xu3, Yu Lin3, Kezhong Liu1, Yanghong Zou2, Qingqing Ye4, Yu Mao5, Wenxiong Chen3, Guangping Zhou2, Huaying Sun6, Hui Huang7, Rui Li3, Gui Li3, Lihong Li3, Qiong Wang3, Qingwei Long3, Hongdi Huang3, Xin Geng2, Yi Liu2, Cirong Liu8, Bing Li9, Zhu Zhou10, Jinghui Li11, Jianhong Wang12. 1. National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Institutes of Physical Science and Information Technology，Anhui University, Hefei, China. 2. First Affiliation Hospital of Kunming Medical University, Kunming, China. 3. National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. 4. Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China. 5. National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; School of Chinese Materia Medica, Yunnan University of Chinese Medicine. Kunming, Yunnan, China. 6. School of Chinese Materia Medica, Yunnan University of Chinese Medicine. Kunming, Yunnan, China. 7. Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. 8. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Shanghai, China. 9. National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address: libing@mail.kiz.ac.cn. 10. First Affiliation Hospital of Kunming Medical University, Kunming, China. Electronic address: zhouzhu21@163.com. 11. First Affiliation Hospital of Kunming Medical University, Kunming, China. Electronic address: km_ljh@126.com. 12. National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address: wangjh@mail.kiz.ac.cn.
Abstract
BACKGROUND: Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans. RESULTS: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke. COMPARISON WITH EXISTING METHODS: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect. CONCLUSIONS: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.
BACKGROUND:Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans. RESULTS: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke. COMPARISON WITH EXISTING METHODS: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect. CONCLUSIONS: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying humanstroke pathology and physiology and for new therapies development.