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SINAPSE experts from around Scotland have developed ten online modules designed to explain medical imaging. They are freely available and are intended for non-specialists.


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Online Short Courses

Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia

Author(s): K. N. Murray, S. Girard, W. M. Holmes, L. M. Parkes, S. R. Williams, A. R. Parry-Jones, S. M. Allan

Abstract:
BACKGROUND AND PURPOSE: Systemic inflammation contributes to diverse acute and chronic brain pathologies, and extensive evidence implicates inflammation in stroke susceptibility and poor outcome. Here we investigate whether systemic inflammation alters cerebral blood flow during reperfusion after experimental cerebral ischemia. METHODS: Serial diffusion and perfusion-weighted MRI was performed after reperfusion in Wistar rats given systemic (intraperitoneal) interleukin-1beta or vehicle before 60-minute transient middle cerebral artery occlusion. The expression and location of endothelin-1 was assessed by polymerase chain reaction, ELISA, and immunofluorescence. RESULTS: Systemic interleukin-1 caused a severe reduction in cerebral blood flow and increase in infarct volume compared with vehicle. Restriction in cerebral blood flow was observed alongside activation of the cerebral vasculature and upregulation of the vasoconstricting peptide endothelin-1 in the ischemic penumbra. A microthrombotic profile was also observed in the vasculature of rats receiving interleukin-1. Blockade of endothelin-1 receptors reversed this hypoperfusion, reduced tissue damage, and improved functional outcome. CONCLUSIONS: These data suggest patients with a raised inflammatory profile may have persistent deficits in perfusion after reopening of an occluded vessel. Future therapeutic strategies to interrupt the mechanism identified could lead to enhanced recovery of penumbra in patients with a heightened inflammatory burden and a better outcome after stroke.

Full version: Available here

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ISBN: 1524-4628 (Electronic) 0039-2499 (Linking)
Publication Year: 2014
Periodical: Stroke
Periodical Number: 11
Volume: 45
Pages: 3412-9
Author Address: From the Faculty of Life Sciences (K.N.M., S.M.A.) and Centre for Imaging Science (L.M.P., S.R.W.), University of Manchester, Manchester, United Kingdom; Sainte-Justine Hospital Research Centre, University of Montreal, Canada (S.G.); Glasgow Experimental MRI Centre, The University of Glasgow, Glasgow, United Kingdom (W.M.H.); and University of Manchester, Manchester Academic Health Sciences Centre, United Kingdom (A.R.P.-J.). From the Faculty of Life Sciences (K.N.M., S.M.A.) and Centre for Imaging Science (L.M.P., S.R.W.), University of Manchester, Manchester, United Kingdom; Sainte-Justine Hospital Research Centre, University of Montreal, Canada (S.G.); Glasgow Experimental MRI Centre, The University of Glasgow, Glasgow, United Kingdom (W.M.H.); and University of Manchester, Manchester Academic Health Sciences Centre, United Kingdom (A.R.P.-J.). adrian.parry-jones@manchester.ac.uk.