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Carleton-Lecture-Animal models stroke and VaD

Carleton-Lecture-Animal models stroke and VaD - Animal...

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Animal’Models:’Stroke/ VaD’ January’27,’2004’
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There’are’two’main’types’of’strokes,’ischemic’and’hemorrhagic’strokes. Adapted’from’( Green’et’al.,’2003 )’.
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Non Modifable Risk Factors Modifable Risk Factors Medical’ Lifestyle’ Age ’ ’ Diabetes’ ’ ’ Smoking’ Gender Hypertension’ Obesity’ Race/ethnicity Atherosclerosis’ Stress’ Prior stroke or TIA 1 High’cholesterol ’ Alcohol’use ’ Atrial’FibrillaJon’(AF) 2 Physical’InacJvity ’ ’ ’ ’ ’ 1 ’Transient’ischemic’aQack’or’silent’stroke 2 ’Cardiac’abnormality’characterized’by’irregular’heart’beat Modifable and non-modifable risk ±actors associated with stroke.
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Animal’disease’models’ Experimental’paradigms’used’to’study’diseases’ Recapitulate’diseases’in’laboratory’seWng’ PlaXorm’for’studying’disease’mechanisms,’ pathophysiology’and’pathogenesis’ Can’be’manipulated’to’study’diFerent’aspects’of’ complex’diseases’and’disorders’ Invaluable’preclinical’tool’for’idenJfying’drug’ targets’ Developing’and’assessing’new’therapeuJc’ intervenJons’
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Stroke’models’ Experimental’models’fall’into’two’general’ categories:’global’and’focal’ischemia’(based’on’ the’type’of’damage’they’produce’ Stroke’have’been’modeled’in’large’and’small’ animals’ Vast’majority’of’stroke’are’modelled’in’small’ rodents’(mice,’gerbils’and’rats)’ Low’cost’of’acquisiJon’and’maintenance’ Easy’to’control’experimental’variables’ Ease’of’surgical’manipulaJon’
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Ischemic’models:’Global’Ischemia’ Involves’near’or’complete’blockade’of’blood’flow’ to’the’enJre’brain’ Produces’wide’spread’injury’to’vulnerable’cell’ populaJon’in’the’brain’including’the’ neocortex,’ striatum’and’hippocampus’ Typically’achieved’via’the’occlusion’of’blood’ vessel(s)’supplying’the’brain,’applicaJon’of’a’ neck’tourniquet’or’decapitaJon’ The’two’(2VO)’and’four’vessel’occlusion’(4VO)’ models’are’most’commonly’used’
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Global’ischemic’model:’2VO’ The’two’common’caroJd’arteries’ are’temporary’occluded’ Produces’near’complete’ischemia’ in’rodent’species’such’as’the’ gerbil’that’lacks’posterior’ communicaJng’arteries’ Five’minute’occlusion’Jme’is’ sufficiently’produces’death’of’ CA1’neurons’ Severity’of’injury’depends’on’ occlusion’Jme’ VariaJon’in’this’model’exists’ e.g’ it’can’be’coupled’with’ hypotension’ Yonekura et al. 2008
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Global’Ischemic’model:’4VO’ Similar’to’the’2VO’model’but’a’liQle’ more’surgically’challenging.’
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Carleton-Lecture-Animal models stroke and VaD - Animal...

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