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Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO.

ABSTRACT: An argument for preclinical stroke research to make more use of the permanent middle cerebral artery occlusion (MCAO) model, rather than transient MCAO, is presented. Despite STAIR recommending permanent MCAO as the primary model, preclinical stroke research has not been listened. In 2012, Hossmann reported that 64% of the treatment studies for MCAO used prompt transient MCAO models and only 36% of the studies used permanent MCAO or gradual transient MCAO (i.e., embolic stroke model). Then, in 2014 and 2015, 88% of published basic science studies on large vessel occlusion used the transient MCAO model. However, this model only represents 2.5-11.3% of large vessel stroke patients. Therefore, the transient MCAO model, which mimics stroke with reperfusion, does not accurately reflect the majority of clinical stroke cases. Thus, once again, the argument for studying permanent MCAO as a primary model is made and supported.

SUBMITTER: McBride DW

PROVIDER: S-EPMC5772000 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO.

McBride Devin W DW Zhang John H JH

Translational stroke research 20170717

An argument for preclinical stroke research to make more use of the permanent middle cerebral artery occlusion (MCAO) model, rather than transient MCAO, is presented. Despite STAIR recommending permanent MCAO as the primary model, preclinical stroke research has not been listened. In 2012, Hossmann reported that 64% of the treatment studies for MCAO used prompt transient MCAO models and only 36% of the studies used permanent MCAO or gradual transient MCAO (i.e., embolic stroke model). Then, in 2 ...[more]

PMID: 28718030

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Project description:BACKGROUND: Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA) ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion. MATERIALS AND METHODS: 18 adult male and female Merino sheep were randomly allocated to one of three groups (n?=?6/gp): 1) sham surgery; 2) permanent proximal MCA occlusion (MCAO); or 3) temporary MCAO with aneurysm clip. All animals had invasive arterial blood pressure, intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel occlusion or sham surgery animals were killed by perfusion fixation. Brains were processed for histopathological examination and infarct area determination. 6 further animals were randomized to either permanent (n?=?3) or temporary MCAO (n?=?3) and then had magnetic resonance imaging (MRI) at 4 h after MCAO. RESULTS: Evidence of ischemic injury in an MCA distribution was seen in all stroke animals. The ischemic lesion area was significantly larger after permanent (28.8%) compared with temporary MCAO (14.6%). Sham animals demonstrated no evidence of ischemic injury. There was a significant reduction in brain tissue oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the permanent MCAO animals with a diffusion deficit involving the whole right MCA territory, whereas temporary MCAO animals demonstrated MRA evidence of flow within the right MCA and smaller predominantly cortical diffusion deficits. CONCLUSIONS: Proximal MCAO can be achieved in an ovine model of stroke via a surgical approach. Permanent occlusion creates larger infarct volumes, however aneurysm clip application allows for reperfusion.

Dataset Information

Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO.

Publications

Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO.

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