A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys,Journal of Neuroscience Methods

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A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys
Journal of Neuroscience Methods ( IF 3 ) Pub Date : 2021-07-20 , DOI: 10.1016/j.jneumeth.2021.109291
Zhiting Zhang ₁ , Shuguo Wang ₂ , Lingli Du ₃ , Ling Xu ₃ , Yu Lin ₃ , Kezhong Liu ₁ , Yanghong Zou ₂ , Bin Li ₄ , Qingqing Ye ₄ , Yu Mao ₅ , Wenxiong Chen ₃ , Guangping Zhou ₂ , Huaying Sun ₆ , Hui Huang ₇ , Rui Li ₃ , Gui Li ₃ , Lihong Li ₃ , Qiong Wang ₃ , Qingwei Long ₃ , Hongdi Huang ₃ , Xin Geng ₂ , Yi Liu ₂ , Cirong Liu ₈ , Bing Li ₃ , Zhu Zhou ₂ , Jinghui Li ₂ , Jianhong Wang ₃

Affiliation

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.
First Affiliation Hospital of Kunming Medical University, Kunming, China.
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.
Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
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.
School of Chinese Materia Medica, Yunnan University of Chinese Medicine. Kunming, Yunnan, China.
Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.
Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Shanghai, China.

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.

中文翻译：

恒河猴光血栓形成中风模型的初步行为和神经影像学研究

背景

缺血性中风导致人类长期残疾，迄今为止尚无有效的临床治疗方法。非人类灵长类动物的大脑中动脉闭塞 (MCAO) 模型已被证明对转化中风研究具有价值。

新方法

在目前的研究中，在大脑中动脉 (MCA) 血栓形成的近端或远端的恒河猴中建立了光血栓 (PT) 中风模型。这项研究是第一个使用行为和生理测量以及 MRI 扫描比较猴子 PT 中风的两种方法的研究。

结果

实验发现，梗塞发生在 MCA 目标区域，所有猴子的行为受损，表现为神经功能缺陷，以及物体检索绕道 (ORD) 任务中的运动和认知。患有远端 MCA 血栓形成的猴子随着外侧裂区、邻近中央前回和中央后回的连续光刺激而发展，在行为方面有类似的损害，并在第 4 天表现出小水肿体积的趋势，近端 MCA 血栓形成和 7 后 PT 行程。