Canadian Stroke Network
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Canadian Stroke Network

Development of pre-clinical stroke models

Project Leader:

Michael Tymianski, Toronto Western Research Institute

Project Team:

R. Loch Macdonald, St. Michael’s Hospital, Toronto
David Mikulis, Toronto Western Research Institute
Michael W. Salter, Hospital for Sick Children
Yu-Tian Wang, University of British Columbia
Andy Tasker, University of Prince Edward Island
Michelle Aarts, University of Toronto
Douglas Cook, Toronto Western Research Institute
Hong Cui, Toronto Western Research Institute
Hong-Shuo Sun, Toronto Western Research Institute
Jinglu Ai, St. Michael’s Hospital
Lucy Teves, Toronto Western Research Institute
Michael D. Hill, University of Calgary
Nicholas Hatsopoulos, University of Chicago

Project Summary:

Among its missions, the CSN is dedicated to translating fundamental research to the point of clinical utility. Since its inception, CSN scientists have studied stroke mechanisms and neuroprotective strategies, of which some are in clinical trials. But progress has been slow because research has been restricted to tools comprising genetic and biochemical assays, cell based assays, and rodent models of stroke. Historically, these tools have failed to translate stroke treatments to human use even though fundamental biology is unlikely to differ between humans and rodents. This indicates that rodents and humans differ at one or more critical levels that cannot be evaluated using current tools. While acknowledged, these unknowns have never been adequately addressed. Thus, the Project Team PIs have agreed to jointly participate in elucidating stroke mechanisms in more relevant models (RM).

The long-term goal is to test the feasibility of treating acute ischemic stroke in RMs. To achieve this, a practical stroke model must be established in which rodents and RMs are evaluated simultaneously at the levels of molecules (e.g., expression of stroke-related genes and proteins), cells (relevant neurophysiological processes), the neurovascular unit, higher levels of anatomical organization and, importantly – surrogate measures of stroke outcome such as imaging and neurobehaviour. The first task is development of an RM of focal ischemic stroke that can be evaluated at all levels of biological organization, but also all surrogate outcome measures used in humans. This proposal provides an unprecedented opportunity in Canada to obtain knowledge on stroke mechanisms in RMs, thus moving basic stroke research as close as possible to the human situation.

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