Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral Circulation and Outcome in Rabbits
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Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral Circulation and Outcome in Rabbits Christopher D. d’Esterre & Kenneth M. Tichauer & Richard I. Aviv & Wolfgang Eisert & Ting-Yim Lee
Received: 9 October 2010 / Revised: 1 December 2010 / Accepted: 22 December 2010 / Published online: 11 January 2011 # Springer Science+Business Media, LLC 2011
Abstract Clinical observations have indicated that secondary treatment with dipyridamole (DIP) may ameliorate stroke severity. The purpose of this study was to explore the effect of pre-stroke DIP treatment on stroke outcome in a rabbit model of embolic occlusion. Twenty male New Zealand white rabbits were randomly selected for intravenous treatment with DIP (n = 10) or saline (n = 10) for 7 days prior to an embolic cerebral occlusion by an autologous blood clot. Multiple computed tomography perfusion scans were acquired out to 28 days post-stroke to map cerebrohemodynamics, in conjunction with neurological assessments and histopathology. The DIP-treated group fared better than the saline group on several C. D. d’Esterre : T.-Y. Lee The University of Western Ontario, London, ON, Canada C. D. d’Esterre : T.-Y. Lee Lawson Health Research Institute, London, ON, Canada C. D. d’Esterre (*) : T.-Y. Lee Robarts Research Institute, Imaging Research Laboratories, 100 Perth Drive, London, ON, Canada N6A 5K9 e-mail: [email protected] K. M. Tichauer Thayer School of Engineering at Dartmouth, Hanover, NH, USA R. I. Aviv Sunnybrook Health Sciences Centre, Toronto, ON, Canada W. Eisert University of Hannover, Hannover, Germany
accounts: 66% of them survived to 28 days, whilst saline animals all had to be euthanized by day 7 due to severe neurological deficits. They presented with significantly more viable tissue in the ischemic hemisphere as well as fewer neurological deficits on days 4 and 7. Furthermore, DIP-treated animals exhibited improved cerebrohemodynamics by 24 h and had less incidence of haemorrhage within their infarcted regions (p < 0.05). DIP treatment prior to stroke onset can significantly improve neurological outcome, cerebral hemodynamics, and final infarct volume. Keywords Ischemia . Neuroprotection . Computed tomography . Dipyridamole Abbreviations DIP Dipyridamole CTP CT perfusion CBF Cerebral blood flow CBV Cerebral blood volume
Introduction Clinical outcome following embolic stroke depends on a timely maintenance of the ischemic penumbra through endogenous regulation and exogenous intervention. Primary stroke treatment with intravenous tissue plasminogen activator is the most widespread method of restoring blood flow to the ischemic lesion; however, it is an aggressive approach that can lead to undesirable complications, primarily hemorrhagic transformation [1]. For this reason, there is much interest in uncovering novel methods for cerebrovascular conditioning before stroke onset.
Transl. Stroke Res. (2011) 2:186–194
Clinical trials have suggested a combination of extended-release dipyridamole (DIP) and low-dose aspirin, both antithrombotic
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