动物模型,脑缺血 z-bo 2020-08-11 531

　　1. Rodent model of global cerebral ischemia

　　Research shows that about 50% of human survivors of cardiac arrest will have permanent motor or cognitive dysfunction. The rodent acute global cerebral ischemia model can simulate the selective brain damage caused by cardiac arrest. At present, gerbils are often used to prepare this model. The gerbil lacks a complete Willis artery ring. The acute global cerebral ischemia model can be made by ligating or clamping the bilateral internal carotid arteries. Reperfusion can be achieved by removing the arterial clamp. The method of making a model of global cerebral ischemia in gerbils is simple. After modeling, the changes of neurons in the hippocampus of gerbils are similar to those in the CA1 area of the hippocampus after cardiac arrest in humans. The pathophysiological process after 24 hours is also very similar. It is widely used in the study of delayed neuronal death and the screening of neuroprotective agents. Electrocoagulation or ligation of bilateral vertebral arteries, and blocking the bilateral common carotid arteries after 24 hours can establish a rodent model of global cerebral ischemia with four-vessel block method. The process of establishing the model by the four-vessel blocking method is to judge the cerebral infarction degree of the model animal through the symptoms and signs after the animal is anesthetized for 24 hours. The model has high stability and sufficient pathological changes. The hippocampus, thalamus, caudate nucleus, and cortical memory areas are severely damaged. It can simulate the pathogenesis of vascular dementia and is mainly used for the evaluation and research of neuroprotective drugs. The white matter damage of the chronic global cerebral ischemia model is similar to the human white matter lesions seen in imaging studies, and it is widely used in the research of white matter damage. The main method is to block the bilateral internal carotid arteries in rats. Although there is a compensation mechanism of the basilar artery and the opening of the collateral circulation in the circle of Willis, it will gradually form a state of chronic whole cerebral hypoperfusion. The white matter damage of this model is similar to that of human leukoaraiosis. The incidence of dementia in model animals is 83%, which is mainly used for the pathophysiological research of dementia. Shibata et al. improved this model. A bilateral carotid artery stenosis model was established. A coil with an inner diameter of 0.18 mm and a length of 2.5 mm was wound around the common carotid artery through rotation, successfully causing the common carotid artery to stenosis. Compared with bilateral carotid artery ligation, the cerebral blood flow of the improved model decreases slowly and does not cause damage to the visual pathway.

　　2. Rodent focal cerebral ischemia model

　　Compared with the global cerebral ischemia model, the focal cerebral infarction model can form a specific part of the cerebral infarction, which has less impact on the whole body. The incidence of spontaneous hypertension is more similar to that of human cerebral infarction. The current application is also more extensive. At present, craniotomy occlusion method, thread embolization method and thromboembolism method are widely used.

　　(1) Craniotomy and occlusion

　　The craniotomy and occlusion method has a reliable effect and good reproducibility. It was once regarded as a standard cerebral ischemia model, but as an invasive model making method, it is easy to damage the brain tissue and requires high surgical skills. Many scholars have used various methods to ligate the middle cerebral artery to prepare rodent cerebral ischemia models. Ma et al. improved the method of electrocoagulation to prepare the model and selected electrocoagulation of the proximal middle cerebral artery to establish a reproducible model of cerebral ischemia in mice, and obtained larger cerebral infarction volume and stable neurological deficits. Kuraoka et al. confirmed that the modeling of the distal end of the blocked middle cerebral artery in mice is more stable than the internal carotid artery ligation, and the mortality of experimental animals is low. It is an ideal method for modeling of cerebral ischemia in mice.

　　(two) thread bolt method

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　　thread embolization method does not require craniotomy, is simple to operate, has a high success rate, ischemic location is constant, and can accurately control the ischemia-reperfusion time. It has replaced craniotomy as the most widely used middle cerebral artery occlusion method. At present, most studies have adopted the method of making the middle cerebral artery occlusion model proposed by Longa et al. Or make a model after making a slight improvement based on this method. Block the branches of the middle cerebral artery, posterior communicating artery, and internal carotid artery. Studies by Woitzik et al. have shown that selective blocking of the middle cerebral artery, posterior communicating artery, and internal carotid artery has good repeatability, but the selective middle cerebral artery occlusion model has a significant increase in infarct volume within 24 hours, which is suitable for neuroprotective drug research . The thread-bolt method model has good repeatability, but confounding factors must still be strictly controlled. Small differences in operation will cause differences in modeling effects. The improvement study of the thread embolization method shows that the pterygopalatine artery is not separated, the traction on the vagus nerve is reduced, and the timely supplement of energy can reduce animal mortality. The diameter and surface coating of the thread plug, especially the smoothness of the end, have a decisive influence on the embolization effect. In previous studies, silicon-coated cords, glue-coated cords, and blunt ends with fused round cords were used. A recent report showed that the modelling success rate of paraffin-coated sutures reached 100%. Compared with naked nylon sutures, the infarct volume was larger and the mortality of model animals was lower. It is a new and reliable middle cerebral artery defect. Method of making blood model.

　　(three) thromboembolism

　　Most human cerebral ischemia originates from thromboembolism. The thromboembolism model is close to the actual situation of human cerebral ischemia, and can be used to explore thrombolytic mechanism and conduct thrombolytic drug research. It has advantages that other models cannot match. Because the sensitivity of the rat fibrinolytic system is lower than that of humans. Previous thrombolytic experiments have used recombinant human tissue plasminogen activator (rt-PA) doses higher than human thrombolytic doses. Recent studies have shown that low-dose (0.9mg/kg) rt-PA thrombolysis after 45 minutes of thromboembolism can recanalize blood vessels, reduce infarct volume and reduce cerebral edema. Another study confirmed that rt-PA (10mg/kg) thrombolysis will increase the infarct volume and the risk of hemorrhagic transformation 4 hours after the preparation of the model. In the past, thromboembolism and thrombolysis models were mainly used in rats. A recent study used mice. A craniotomy was performed through the temporal lobe, and thrombin was injected into the middle cerebral artery, causing in situ thrombosis and successful thrombolysis. The method has high repeatability in terms of infarction formation, blood flow blockage and neurological deficits, and successfully thrombolysis has opened up a new field of mouse thromboembolism-thrombolysis model.