Abstract
Background and purposeReliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model.MethodsThirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. The site of occlusion was demonstrated by arteriography. Following histological preparation and evaluation, the size of the hemispheres and the infarcts were measured by quantitative histology and planimetry. Another parallel stroke model study was subsequently examined to investigate if the conclusions from the first study could be applied to the second study.ResultsThe median size of the infarct was 40% of the ipsilateral hemisphere in both the 19 animals with occlusion localised to the intracranial part of the internal carotid artery and in the 11 animals where the main trunk of the middle cerebral artery was occluded. In 5 animals, occlusion of the extracranial part of the internal carotid artery resulted in significantly smaller infarcts compared to other groups (p < 0.01). Another independent study re-confirmed these results. Furthermore, significant correlations (R > 0.76, p < 0.0001) were found between 1) cortical, subcortical, and total infarct volumes, 2) oedema in percent of the left hemisphere, 3) clinical score before termination and 4) postoperative weight loss.ConclusionsDistal occlusions of the intracranial part of the internal carotid or middle cerebral arteries resulted in comparable large sized infarctions and oedema. This indicates that investigators do not need a similar number of such occlusions in each experimental group. Contrary to observations in the clinic, distal internal carotid artery occlusions did not result in worse outcome than middle cerebral stem occlusions, but this finding may be explained by the controlled emboli size in this experimental stroke model.
Highlights
Commonly human stroke patients suffer from direct occlusion of the middle cerebral artery (MCAO), or from occlusions of the internal carotid artery (ICAO), which reduce or prevent sufficient blood flow through the middle cerebral artery (MCA)
On the final blinded evaluation of the arteriograms the surviving animals were divided into 3 different subgroups: one subgroup of 11 animals had a grade 2 occlusion, a second subgroup of 19 animals had a grade 3 occlusion and the remaining subgroup of 5 animals had a grade 4 occlusion
The lack of infarct volume differences when comparing animals with a grade 2 or 3 occlusion may seem contrary to clinical findings, where distal ICA occlusions have been associated with a worsening of outcome compared to MCA stem occlusions [17,18,19]
Summary
Human stroke patients suffer from direct occlusion of the middle cerebral artery (MCAO), or from occlusions of the internal carotid artery (ICAO), which reduce or prevent sufficient blood flow through the middle cerebral artery (MCA).Recently, the importance of establishing reliable animal models is clear, as hundreds of effective neuroprotective therapies in animals failed to show beneficial efficacy in rats before benefit of human thrombolytic treatment was documented [3,4,5]. The main purpose of this study was to investigate the relationship between the site of arterial occlusion and the subsequent size of the resulting infarct in a rat embolic stroke model. In this study we investigated several aspects associated to the embolic location, namely infarct volume, oedema size, mortality and effects of re-embolization. In the present study, the consequences of emboli localisation especially upon infarct volume were investigated for the first time and further related to both the formation of oedema and the clinical outcome. Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model
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