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High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

Background: Irreversible damage may occur at reperfusion after sustained cerebral ischaemia., Aims: We investigated the value of cyclosporine A for reducing the infarct size in a model of transient middle cerebral artery occlusion., Methods: Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during occlusion to confirm the success of surgery and measure baseline lesion size. Animals were randomly treated by: (i) intracarotid cyclosporine A (10 mg/kg) 20 mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10 mg/kg) immediately after reperfusion (post-treatment group); and (iii) intracarotid saline immediately after reperfusion., Results: Histopathological measurements on day 1 showed a significant reduction of infarct size in the pretreatment group compared to the post-treatment (percentage values of ipsilateral hemispheres: 16 ± 5% vs. 29 ± 11%, P = 0·004) and saline groups (16 ± 5% vs. 42 ± 12%, P = 0·015). No significant difference was observed between the post-treatment and saline groups (P = 0·065). Behavioural examinations on day 1 showed no significant difference between groups. Immunohistochemistry showed a statistically significant reduction of microglial cell count in the pretreatment group compared to either saline or cyclosporine A post-treatment groups., Conclusions: We conclude that intracarotid cyclosporine A is effective in reducing infarct size when given prior to ischaemia, but not when administered at reperfusion., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background: Models of intraluminal middle cerebral artery occlusion present an intrinsic variability in infarct size. Behavioral evaluation is frequently performed during arterial occlusion to confirm success of surgery., Aims And/or Hypothesis: We compared the value of behavioral testing and multimodal magnetic resonance imaging performed during arterial occlusion for identifying successfully operated animals., Methods: Rats were tested with behavioral assessment (using three scoring scales and the adhesive removal test) and multimodal magnetic resonance imaging (including magnetic resonance angiography, diffusion-weighted and perfusion-weighted imaging), both performed during the two-hours of middle cerebral artery occlusion using the intraluminal suture model. Behavioral assessment was repeated 24 h after reperfusion, followed by sacrifice., Results: Acute apparent diffusion coefficient lesion volume was correlated with both 2,3,5-triphenyl tetrazolium chloride infarct size (r = 0·75, P = 0·02) and behavioral status (r = 0·66, P = 0·05) on day one. Conversely, no correlation was found between acute behavioral examination and day one outcomes (2,3,5-triphenyl tetrazolium chloride infarct volume, r = 0·40, P = 0·28; behavioral examination, r = 0·39, P = 0·30). Day zero apparent diffusion coefficient volumes (P = 0·04), but not behavioral assessment (P = 0·60), discriminated animals with day one corticostriatal infarcts from these with subcortical infarcts., Conclusions: Acute behavioral testing performed during arterial occlusion fails to identify successfully operated animals. Acute diffusion magnetic resonance imaging may be more appropriate to assess and reduce infarct size variability in this model., (© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.)