動物腦缺血模型

1、動物腦缺血模型第1頁，共11頁，2022年，5月20日，21點12分，星期一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

2、 subgroups represented by the animal models should be targeted 第2頁，共11頁，2022年，5月20日，21點12分，星期一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 n

3、ew therapies for stroke.第3頁，共11頁，2022年，5月20日，21點12分，星期一Several recent animal models have been designed specificallyto address specific risk factors, to determine neuralrepair processes, to test new neuroprotective and recanalizingstrategies.第4頁，共11頁，2022年，5月20日，21點12分，星期一Today reliable animal models

4、 for stroke areavailable in a variety of species including primates, pigs,sheep, dogs, cats, mongolian gerbils, rabbits, rats and mice.第5頁，共11頁，2022年，5月20日，21點12分，星期一Global modelsTwo-vessel occlusion model in gerbil Transient bilateral occlusion of common carotidsTwo-vessel occlusion model in rat Tr

5、ansient bilateral occlusion of common carotids plus hypotension (-50 mmHg) Four-vessel occlusion model in rat Transient bilateral occlusion of common carotids plus permanent bilateral occlusion of vertebral arteriesMiscellaneous Cardiac arrest Decapitation Neck Tourniquet Elevated cerebrospinal flui

6、d pressure第6頁，共11頁，2022年，5月20日，21點12分，星期一The simplest, and therefore most popular, global model for screening novel neuroprotectants is the 2 vessel occlusion in gerbils. Bilateral occlusion of the common carotids in this model is sufficient to produce severe forebrain ischaemia, because gerbils lac

7、k posterior communicatingarteries (PComA) necessary to complete the circle of Willis which, in humans and rats, permits collateral blood flow.第7頁，共11頁，2022年，5月20日，21點12分，星期一The 4-vessel occlusion rat model is a more difficult surgical procedure.A day before the carotids are occluded, the anterior ve

8、rtebrals arepermanently occluded by electrocauterization. This is often a source oferror. Either the vertebrals are insufficiently occluded or the Cl vertebrateis excessively heated, resulting in damage to the medulla and an increasein the mortality resulting from surgery because the animals experie

9、ncerespiratory difficulties.第8頁，共11頁，2022年，5月20日，21點12分，星期一The delayed and selective death following global ischaemia has beenwell characterized and is similar among all global models. Thehistopathology varies with the duration of ischaemia. With a relativelybrief insult of 10 min, there is selectiv

10、e damage to the CA1 region of thehippocampus which occurs from about 3-7 days第9頁，共11頁，2022年，5月20日，21點12分，星期一Focal modelsPimumnt or transientMiddle cerebral artery occlusion (MCAO) - methods of occlusion clip, ligature,intraluminar thread (coated/uncoated), cauterization (not transient)Use of spontan

11、eously 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 Injection into internal carotid arteryInjection of platelet aggregates into common carotidInjection of small blood clots into common carotid (transient if followed by tPA)第10頁，共11頁，2022年，5月20日，21點12分，星期一At the same time, those designing clinical trials should focus ontargeting stroke of the types best represente