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Content archived on 2024-05-29

Mechanisms of cerebral preconditioning

Objective

Despite increasing knowledge about stroke, treatment options remain unsatisfactory. Because the transfer of neuroprotective agents from the animal model to the patient has turned out to be problematic, there is tremendous interest in new ways of neuroprotection that might be feasible in humans also, such as the induction of endogenous cerebral protection. These mechanisms have been shown to be inducible by a sublethal toxic stimulus in vitro and in animal models ("preconditioning", "Ischemic tolerance"). In a recent study on stroke patients with antecedent transient ischemic attacks, the applicant found evidence for the existence of ischemic tolerance in the human brain.

The proposed project will address the following questions:
1) What factors elicited by preconditioning cause ischemic protection?
2) Is there a specific tissue ¿signature¿ of preconditioned tissue?
3) What distinguishes preconditioned tissue in a following ischemia from first ever ischemic brains?

Magnetic Resonance Imaging (MRI) will be applied to a rat model of hypoxic preconditioning and focal ischemia, to assess parameters of cerebral perfusion and tissue integrity and their spatial and temporal relation to the development of tolerance. To identify a vascular component of preconditioning, MRI at 7 Tesla will include highly sophisticated arterial spin labelling techniques for perfusion-weighted imaging, developed at the host institution. Co-registered histological data will provide information on the extent and character of ischemia-induced neuro genesis.

This comprehensive approach will allow addressing our principal hypothesis: induction of ischemic tolerance is facilitated by a concerted process of protective mechanisms on cellular and vascular level, rather than by independent single events. The transfer of expertise to the Berlin Neuroimaging Centre will provide new MRI technology and exciting options for co-operation, thereby contributing to European science competitiveness.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-6
See other projects for this call

Funding Scheme

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OIF - Marie Curie actions-Outgoing International Fellowships

Coordinator

UNIVERSITAET ZUERICH
EU contribution
No data
Total cost

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No data

Participants (2)