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Coxsackievirus B3 HFMD animal models in Syrian hamster and Rhesus Monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and Rhesus Monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,Rhesus Monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild Rhesus Monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus Monkey

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Comparative study of the transfection efficiency of commonly used viral vectors in Rhesus Monkey (Macaca mulatta) brains

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Zoological Research 2017年第2期38卷 88-95页

作者： Shi-Hao Wu Zhi-Xing Liao Joshua D. Rizak Na Zheng Lin-Heng Zhang Hen Tang Xiao-Bin He Yang Wu Xia-Ping He Mei-Feng Yang Zheng-Hui Li Dong-Dong Qin Xin-Tian Hu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China Nerve System Coding Discipline Group Kunming College of Life Science University of the Chinese Academy of Sciences Kunming Yunnan 650000 China Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China Department of Anatomy and Histology & Embryology Faculty of Basic Medical Science Kunming Medical University Kunming Yunnan 650500 China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai 200031 China Center for Excellence in Brain Science Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan Hubei 430071 China

Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four Rhesus Monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates （NHPs）. These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.

关键词： Recombinant adeno-associated virus Lentivirus Rhesus Monkey Central nervous system

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Tissue-engineered Rhesus Monkey nerve grafts for the repair of long ulnar nerve defects:similar outcomes to autologous nerve grafts

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Neural Regeneration Research 2016年第11期11卷 1845-1850页

作者： Chang-qing Jiang Jun Hu Jian-ping Xiang Jia-kai Zhu Xiao-lin Liu Peng Luo Department of Sports Medicine and Rehabilitation Peking Universtiy Shenzhen Hospital Shenzhen Guangdong Province China Department of Microscopy First Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong Province China The Sixth People's Hospital of Shenzhen City Shenzhen Guangdong Province China

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in Rhesus Monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult Rhesus Monkeys and seeded with allogeneic Schwann cells. Pathomo- rphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the Rhesus Monkey. The outcomes are similar to those obtained with autologous nerve graft.

关键词： nerve regeneration peripheral nerve injury tissue engineering Rhesus Monkey ulnar nerve chemical extraction allogenic nerve autologous nerve transplantation Schwann cells neural regeneration

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Rhesus Monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions

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Neural Regeneration Research 2016年第9期11卷 1464-1470页

作者： Li-juan Ye Hui Bian Yao-dong Fan Zheng-bo Wang Hua-lin Yu Yuan-ye Ma Feng Chen Department of Pathology Third Affiliated Hospital of Kunming Medical University Kunming Yunnan Province China Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan Province China Department of Physiology Kunming Medical University Kunming Yunnan Province China Second Department of Neurosurgery First Affiliated Hospital of Kunming Medical University Kunming Yunnan Province China Department of Radiology Hainan General Hospital Haikou Hainan Province China

Rhesus Monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus Monkey neural stem cells （1 ×10^5 cells/μL） were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-la- beled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that Rhesus Monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

关键词： nerve regeneration Rhesus Monkey neural stem cells hippocampal lesion cell transplantation spatial learning and memory abilities neural regeneration

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Sleeve bridging of the Rhesus Monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

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Neural Regeneration Research 2015年第1期10卷 53-59页

作者： Yu-hui Kou Pei-xun Zhang Yan-hua Wang Bo Chen Na Han Feng Xue Hong-bo Zhang Xiao-feng Yin Bao-guo Jiang Department of Trauma and Orthopedics Peking University People’s Hospital

Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple ampli- fication of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple ampli- fication of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus Monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were su- tured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of Rhesus Monkey. Neurophysiological examination showed that motor nerve conduction veloc- ity reached 22.63 _＋ 6.34 m/s on the affected side of Rhesus Monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ＋ 652 in the branches of pronator teres of donor, and 2,661 ~ 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

关键词： nerve regeneration peripheral nerve Rhesus Monkey muscular branches of pronator teres ulnar nerve multiple amplification small gap sleeve bridging NSFC grants neural regeneration

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Characteristics of diffusion-tensor imaging for healthy adult Rhesus Monkey brains

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Neural Regeneration Research 2013年第31期8卷 2951-2961页

作者： Xinxiang Zhao Jun Pu Yaodong Fan Xiaoqun Niu Danping Yu Yanglin Zhang Department of Radiology Second Affiliated Hospital of Kunming Medical University Department of Neurosurgery Second Affiliated Hospital of Kunming Medical University Department of Neurosurgery Third Affiliated Hospital of Kunming Medical University Department of Pneumology Second Affiliated Hospital of Kunming Medical University Yiwu Hospital Affiliated to Zhejiang University School of Medicine

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum （splenium and genu） as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy Rhesus Monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old Rhesus Monkeys are similar to those of healthy young people.

关键词： neural regeneration neuroimaging Rhesus Monkey fractional anisotropy brain white matter graymatter MRI diffusion-tensor imaging grants-supported paper neuroregeneration

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Percutaneous transhepatic portal catheterization guided by ultrasound technology for islet transplantation in Rhesus Monkey

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Hepatobiliary & Pancreatic Diseases International 2012年第2期11卷 154-159页

作者： Feng Gao,Shao-Dong Ai,Sheng Liu,Wen-Bin Zeng and Wei Wang Cell Transplantation & Gene Therapy Institute and Department of Ultrasound , Third Xiangya Hospital School of Pharmaceutical Sciences , Central South University, Changsha 410013, China Cell Transplantation & Gene Therapy Institute Central South University Changsha 410013 China Department of Ultrasound Third Xiangya Hospital Central South University Changsha 410013 China School of Pharmaceutical Sciences Central South University Changsha 410013 China

BACKGROUND:Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes.Testing in nonhuman primate models is necessary before clinical application in humans.Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy.In this paper,we describe a new method of percutaneous transhepatic portal catheterization(PTPC) as an alternative to current methods of islet transplantation in Rhesus Monkeys.METHODS:We performed ultrasound-guided PTPC in five adult Rhesus Monkeys weighing 7-8 kg,with portal vein catheterization confirmed by digital subtraction angiography.We monitored for complications in the thoracic and abdominal cavity.To evaluate the safety of ultrasound-guided PTPC,we recorded the changes in portal pressure throughout the microbead transplantation procedure.RESULTS:Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys.Differences in the hepatobiliary anatomy of Rhesus Monkeys compared to humans led to a higher initial complication rate.The first monkey died of abdominal hemorrhage 10 hours post-transplantation.The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures.After gaining experience with the first two monkeys,we decreased both the hepatic puncture time and the number of puncture attempts required,with the remaining three monkeys experiencing no complications.Portal pressures initially increased proportional to the number of transplanted microbeads but returned to preinfusion levels at 30 minutes post-transplantation.The changes in portal pressures occurring during the procedure were not significantly different.CONCLUSIONS:Ultrasound-guided PTPC is an effective,convenient,and minimally invasive method suitable for use in non-human primate models of islet cell transplantation provided that care is taken with hepatic puncture.Its advantages

关键词： ultrasound-guided portal venous catheterization islet xenotransplantation Rhesus Monkey

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Establishment of a Rhesus Monkey model of middle cerebral artery ischemia and reperfusion using a microcatheter embolization method

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Neural Regeneration Research 2010年第15期5卷 1161-1165页

作者： Jie Yang Jian Guo Hongbo Zheng Muke Zhou Li He Wenying Cao Li Xiao Jiachuan Duan Qiyong Gong Xiaoqi Huang Hongxia Li Li Wang Jingqiu Cheng Department of Neurology West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China Huaxi MR Research Center Department of Radiology West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China Laboratory of Transplant Engineering and Immunology West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China

Nonhuman primates are closest to humans in terms of lineage, and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans. Therefore, nonhuman primates could be utilized to simulate the process of ischemic stroke in the human. Few studies, however, have reported the use of endovascular technology to establish a Rhesus Monkey stroke model. In the present study, seven adult, male, Rhesus Monkeys were selected and, following anesthesia, a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow, thereby resulting in middle cerebral artery occlusion. After 2 hours, the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion. Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery. Magnetic resonance imaging revealed the existence of ischemic brain lesions, and neurological examination showed sustained functional deficits following surgery. The Rhesus Monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility. The scope and degree of ischemic damage using this model was controllable. Therefore, this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.

关键词： ischemia reperfusion middle cerebral artery microcatheter magnetic resonance imaging Rhesus Monkey brain injury neural regeneration

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Characterization of the Sweet Taste Receptor Tas1r2 from an Old World monkey Species Rhesus Monkey

Characterization of the Sweet Taste Receptor Tas1r2 from an ...

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中国生物化学与分子生物学会2016年全国学术会议

作者： Weiwei Zheng Meng Zhao Chenggu Cai Bo Liu Department of Food Science and Engineering Qilu University of Technology Department of Bioengineering Qilu University of Technology Department of Biochemistry and Molecular Biology School of Medicine Shandong University

Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2(taste receptor type 1 member 2)and Tas1r3(taste receptor type 1 member 3).Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor.In this study,we cloned,expressed

关键词： sweet taste receptor Rhesus Monkey Tas1r2/Tas1r3 perillartine amiloride molecular modeling

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Application and Assessment of Ketamine-Xylidinothiazoline Combinations for Anaesthesia in Rhesus Monkey

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Journal of Northeast Agricultural University(English Edition) 2009年第1期16卷 45-50页

作者： XIAO Jianhua GAO Li Liu Huanqi FAN Honggang MA Haikun LIU Yun WANG Hongbin College of Veterinary Medicine Northeast Agricultural University Harbin 150030 China College of Animal Science Qingdao Agricultural University Qingdao 266109 Shandong China

The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketamine-xylidinothiazoline in Rhesus Monkey. Total 20 healthy adult Rhesus Monkeys were divided into two groups and anaesthetized using either intramuscular （IM） ketamine （20 mg·kg^-1） or ketamine （5 mg·kg^-1 IM） and xylidinothiazoline （1 mg·kg^-1 IM）. During anaesthesia rectal temperature, respiratory rate, heart rate, saturation of blood oxygen and blood pressure were recorded. The degree of sedation, analgesia, muscle relaxation were monitored either. The results showed that ketamine alone did not produce adequate anaesthesia, and the combination of xylidinothiazoline and ketamine provided adequate anesthesia for Rhesus Monkeys with no significant side effects and little effects on respiration and circulation.

关键词： anaesthesia Rhesus Monkey ketamine xylidinothiazoline

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