Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (35): 5625-5631.doi: 10.3969/j.issn.2095-4344.2922

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Pathological and behavioral changes after ischemic stroke in adult mice

Liang Yanfeng1, Hao Peng1, Duan Hongmei1, Zhao Wen1, Gao Yudan1, Li Xiaoguang1, 2, Yang Chaoyang1   

  1. 1Department of Neurobiology, Capital Medical University, Beijing 100069, China; 2School of Biological and Medical Engineering, Beijing Laboratory of Biomaterials and Nerve Regeneration, Big Data Precision Medical Center for Advanced Innovation, Beihang University, Beijing 100191, China

  • Received:2020-02-25 Revised:2020-03-03 Accepted:2020-04-23 Online:2020-12-18 Published:2020-10-17
  • Contact: Yang Chaoyang, MD, Professor, Department of Neurobiology, Capital Medical University, Beijing 100069, China
  • About author:Liang Yanfeng, Master, Department of Neurobiology, Capital Medical University, Beijing 100069, China
  • Supported by:
    the National Key Research and Development Projects of China, No. 2017YFC1104002 and 2017YFC1104001; the National Natural Science Foundation of China, No. 81941011, 31730030, 31650001, 31320103903, 31670988, 31971279 , 31771053; Beijing Science and Technology Plan, No. Z181100001818007; 2018 Key Science and Technology Plan of Beijing Municipal Education Commission, No. KZ201810025030

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Abstract:

BACKGROUND: A rat model of middle cerebral artery embolization can cause stable focal cortical infarction, and it has a low mortality rate while simulating the pathological state of human stroke. However, there are high requirements on the skills and equipment and a later evaluation is necessary to determine the success of modeling.

OBJECTIVE: To establish an effective, stable and simple ischemic stroke model, to reveal pathological changes in infarcted and surrounding areas after stroke in mice, and to explore behavioral changes after stroke in mice.

METHODS: Permanent electrocoagulation of the distal middle cerebral artery in mice was condcted. Twenty-four hours later, 2,3,5-triphenyltetrazolium chloride staining was used to determine the infarct size of the model and to calculate the success rate of the model. Hematoxylin-eosin staining was performed on brain tissue sections at different time points (1, 3, 7, 10, 14 days) after occlusion of the distal middle cerebral artery in mice to observe volume changes of the ischemic necrosis area with time. Immunohistochemical staining of glial fibrillary acidic protein and Iba-1 was performed to detect the changes of glial reaction and inflammatory reaction after brain injury in model mice. Finally, grid foot error test and cylinder test were used to evaluate the loss of sensorimotor function after stroke.

RESULTS AND CONCLUSION: Focal cortical infarction was caused after distal middle cerebral artery occlusion. The mortality rate of this new model was only 9% and the success rate was 87%. Infarction was mainly located in M1/S1/S2 area, and the infarcted range was stable after 10 days of occlusion. The inflammatory response peaked on the 3rd day of stroke, and a stable astroglial scar was formed around the injury area on the 14th day. After focal cortical infarction, the contralateral limbs of mice showed obvious loss of sensory and motor functions. To conclude, sensory and motor functions deficits occur immediately after stroke in experimental mice and persist until 12 weeks after stroke. The new model of distal middle cerebral artery occlusion is a stable, reliable model, with a clear infarct range, which is suitable for the study of ischemic stroke.


Key words: stroke, ischemic stroke, middle cerebral artery, distal occlusion, pathological changes, behavior, model, mouse

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