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Novel Genes Induced during Ischaemic Tolerance


The objective of this proposal is to identify genes which may influence the outcome following an ischemic event in the brain.

Using molecular biological methods, genes that are induced in the rat during an induced non-lethal brief ischemic event which generates 'ischemic tolerance' will be delineated and their products will be studied. These genes and their products might engender neuroprotection.

Ischemic tolerance has been described in the gerbil and the rat, employing the 4-vessel occlusion model. The aim is to characterize the phenomenon of ischemic tolerance using the 2-vessel occlusion model in the rat by employing state-of-the-art molecular biological methods to reveal changes in gene expression during the 'protective' period. Subtractive cDNA libraries will be constructed from RNA isolated from the brains of treated rats (sublethal ischemia of 2 min duration, brains collected at 6 hr intervals between 24-48hrs after reperfusion) and cloned sequences will be analyzed. Time course of induction and nature of sequence will reveal 'candidate genes' for neuroprotection. These studies will be complemented by in situ hybridization in brain sections of treated and control rats. Ultimately, the control of the expression of these candidate genes and the activity of their protein products will be assessed with respect to neuroprotection against ischemic insults.

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Ruprecht-Karls-Universität Heidelberg
EU contribution
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69120 Heidelberg

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