动物脑缺血模型精.ppt

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1、动物脑缺血模型第1页，本讲稿共11页Animal models of cerebral ischaemia mimic at best less than 25%of all strokes.Compounds which prove efficacious in animal models should,therefore,only beexpected to improve outcome in a quarter of all strokes.If trials for acute strokeare to succeed,stroke subgroups represented by

2、the animal models should be targeted 第2页，本讲稿共11页From the late 1970s,animal models of cerebral ischemiawere developed with the aim of identifying mechanisms thatcause tissue damage and to provide the basis for the development,at a preclinical level,of new therapies for stroke.第3页，本讲稿共11页Several recen

3、t animal models have been designed specificallyto address specific risk factors,to determine neuralrepair processes,to test new neuroprotective and recanalizingstrategies.第4页，本讲稿共11页Today reliable animal models for stroke areavailable in a variety of species including primates,pigs,sheep,dogs,cats,m

4、ongolian gerbils,rabbits,rats and mice.第5页，本讲稿共11页Global modelsTwo-vessel occlusion model in gerbil Transient bilateral occlusion of common carotidsTwo-vessel occlusion model in rat Transient bilateral occlusion of common carotids plus hypotension(-50 mmHg)Four-vessel occlusion model in rat Transien

5、t bilateral occlusion of common carotids plus permanent bilateral occlusion of vertebral arteriesMiscellaneous Cardiac arrest Decapitation Neck Tourniquet Elevated cerebrospinal fluid pressure第6页，本讲稿共11页The simplest,and therefore most popular,global model for screening novel neuroprotectants is the

6、2 vessel occlusion in gerbils.Bilateral occlusion of the common carotids in this model is sufficient to produce severe forebrain ischaemia,because gerbils lack posterior communicatingarteries(PComA)necessary to complete the circle of Willis which,in humans and rats,permits collateral blood flow.第7页，

7、本讲稿共11页The 4-vessel occlusion rat model is a more difficult surgical procedure.A day before the carotids are occluded,the anterior vertebrals arepermanently occluded by electrocauterization.This is often a source oferror.Either the vertebrals are insufficiently occluded or the Cl vertebrateis excess

8、ively heated,resulting in damage to the medulla and an increasein the mortality resulting from surgery because the animals experiencerespiratory difficulties.第8页，本讲稿共11页The delayed and selective death following global ischaemia has beenwell characterized and is similar among all global models.Thehis

9、topathology varies with the duration of ischaemia.With a relativelybrief insult of 10 min,there is selective damage to the CA1 region of thehippocampus which occurs from about 3-7 days第9页，本讲稿共11页Focal modelsPimumnt or transientMiddle cerebral artery occlusion(MCAO)-methods of occlusion clip,ligature

10、,intraluminar thread(coated/uncoated),cauterization(not transient)Use of spontaneously hypertensive rats(SHR)-produces more consistentinfarct with MCAOPermanent-embolism and thrombosis modelsPhotochemical thrombosis using Rose Bengal(produces a core and no penumbra,not transient)Carbon microsphere I

11、njection into internal carotid arteryInjection of platelet aggregates into common carotidInjection of small blood clots into common carotid(transient if followed by tPA)第10页，本讲稿共11页At the same time,those designing clinical trials should focus ontargeting stroke of the types best represented by the models currently in use,rather than anticipating a panacea from every compound which has been found to reduce infarct volume by 20%in a rodent.第11页，本讲稿共11页