Inapparent hemodynamic insufficiency exacerbates ischemic damage in a rat microembolic stroke model

Background and Purpose-Patients with severe carotid artery stenosis may have more severe ischemic damage after embolic stroke than patients without this abnormality. Unilateral proximal carotid occlusion (UCO) alone typically does not induce infarction in normotensive rats. The aim of this study was to investigate whether UCO increases infarct size after microembolic, experimental stroke. Methods-Microembolic infarction was induced in 2 groups of Sprague-Dawley rats by injecting 2000 microspheres (50-mu m diameter) intracranially from the external carotid artery. The common carorid artery (CCA) was either ligated just after the injection (CCA occlusion group, n = 8) or left intact (CCA open group, n = 8). In the control group (n = 4), vehicle without microspheres was injected and the CCA was ligated. Twenty-four hours later, the brains were removed and infarct volumes measured. Perfusion-weighted imaging was used to evaluate the cerebral circulation before and after CCA occlusion with and without microsphere injection in a separate group of animals (n = 16). Results-All animals in the microemboli groups survived and had only a slight hemiparesis 24 hours after occlusion. No neurological deficits were observed in the control group. Infarct volumes were 145+/-57 mm(3) in the CCA occlusion group and 45+/-26 mm(3) in the CCA open group (P < 0.01). There were no infarctions detected in the control group. Perfusion-weighted imaging showed that cerebral blood flow decreased after the CCA occlusion in both experiments with and without the microsphere injection. Conclusions-UCO alone does not induce ischemic damage, but it worsens ischemic lesion size after multiple microemboli. This is probably due to the slight cerebral perfusion insufficiency caused by UCO. These results suggest that patients with cerebral hemodynamic insufficiency, such as those with severe carotid stenosis, may have increased ischemic damage after microembolic events.