动物造模,药效评价,脑缺血 z-bio 2024-08-21 361

　　The phenomenon of cerebral ischemic tolerance refers to the pre production of sublethal ischemia in the brain. This increases the tolerance of brain neurons to subsequent lethal ischemia, thereby preventing the occurrence of delayed neuronal death after cerebral ischemia and providing protection against damage caused by cerebral ischemia.

　　Kitagawa et al. found in a model of forebrain ischemia in sand rats in 1990 that blocking the blood flow of bilateral carotid arteries for 5 minutes can cause constant delayed necrosis of hippocampal CA1 neurons. If a brief, non fatal cerebral ischemia is given 2 minutes in advance, it can partially protect against severe fatal cerebral ischemia 1-7 days later; If a brief ischemia of 2 minutes is given twice with an interval of 1 day, almost complete protection can be achieved, and this phenomenon is called ischemic tolerance. Transient cerebral ischemia given in advance is called ischemic preconditioning.

　　The mechanism of ischemic tolerance is currently unclear and may involve various factors, including excitatory amino acids, adenosine, new gene products (such as the synthesis of new RNA and proteins, upregulation of ultra early gene expression, increased expression of antioxidant enzymes and multiple growth factors in brain tissue, etc.), depolarization, energy metabolism, glial cells, apoptosis and apoptosis inhibitor gene products, heat shock proteins, etc. The cerebral ischemic tolerance model can be used to study the mechanism of this phenomenon and provide a basis for clinical treatment.

　　Animal models of cerebral ischemic tolerance include: whole brain whole brain model, focal whole brain model, whole brain focal model, and focal focal focal model. The preparation method of the model refers to the corresponding cerebral ischemia model in the "Stroke" chapter, and the key to preparing cerebral ischemic tolerance is ischemic pretreatment.

　　It is necessary to limit the first ischemia time and the interval between two ischemia events in the whole brain whole brain model. After 2 minutes of pre ischemia, reperfusion for 1 day can induce ischemic tolerance. The phenomenon of ischemic tolerance can last for 2 days. This model uses selective death of hippocampal CA1 neurons as a morphological observation indicator.

　　Focal whole brain model was performed with middle cerebral artery occlusion (MCAO) for 20 minutes, followed by reperfusion, and then global cerebral ischemia (bilateral carotid artery occlusion and hemorrhagic hypotension induction) was performed every 24 hours. Pathological observation showed a significant decrease in the number of necrotic neurons in the ipsilateral middle cerebral artery supply area. Focal ischemia also has a protective effect on ipsilateral hippocampal neurons outside of focal ischemia, which may be related to the ultra early expression and depolarization of certain genes within the neurons.

　　The whole brain focal model uses the four vessel occlusion method to perform two 6-minute global cerebral ischemia followed by reperfusion, which can reduce the infarct area of MCAO after 18 hours. Cerebral infarction includes both neuronal and non neuronal necrosis, so this model suggests that glial cells, vascular cells, and nerve cells may all be involved in the development of ischemic tolerance.

　　The optimal method for local ischemic preconditioning in focal focal models is to perform 3 sessions of 10 minutes each. It can reduce the infarct area by approximately 30%, and ischemic tolerance occurs 2 days after ischemic preconditioning and lasts for 5-7 days.