Microsoft Word - DMM029108.docx

Animal models are critical for understanding the pathology of stroke and investigating potential treatments. However, in vivo stroke models are associated, particularly in mice, with high variability in lesion volume. We investigated whether a surgical refinement where reperfusion is not reliant on the Circle of Willis reduced outcome variability. Mice underwent 60 minutes of transient middle cerebral artery occlusion avoiding ligation of the external carotid artery. During reperfusion the common carotid artery was either ligated (standard approach), or it was repaired to allow re-establishment of blood flow through the common carotid artery. All mice underwent MRI scanning for assessment of infarct volume, apparent diffusion coefficient and fractional anisotropy along with terminal assessment of infarct volume by TTC staining. Repairing the common carotid artery following middle cerebral artery occlusion enhanced reperfusion (P < 0.01) and reduced the variability seen in both total (histological analysis, P =0.008; T2-weighted MRI, P = 0.015) and core (diffusion tensor imaging MRI scanning, P = 0.043) lesion volume. Avoiding external carotid artery ligation may improve animal wellbeing, through reduced weight loss, while using an alternative surgical approach which enabled reperfusion through the common carotid artery decreased the variability in lesion volume seen within groups. D is ea se M o de ls & M ec ha ni sm s • D M M • A dv an ce a rt ic le