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RESEARCH PRODUCT

Temporal profile of gene induction after venous ischemia accompanied by spreading depression as compared to spreading depression alone

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Abstract The occlusion of two adjacent cortical veins is followed by a widespread reduction of rCBF and the occurrence of small infarcts, which become larger if spreading depression (SD) occurs. The model appears to be useful for studying penumbra pathophysiology. Here, the time course of gene expression in the penumbra was compared to those induced by the SD alone. In an experiment involving rats, an occlusion of two cortical veins was induced by i.v. rose bengal and fiberoptic illumination. Ten SDs were induced at 7-min intervals. Changes of the gene expression after 2, 8, 24 and 72 h were analysed for 13 genes by RT-PCR. The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used for normalization, and expression patterns were studied by cluster analysis. c-fos, cox-2 and bcl-2 responded early (2 h) and far more after the two-vein occlusion with plus SD than after the experiment with SD alone. Secondly, HO-1 and c-myc were increased 24 h after SD was carried out in animals without ischemia. These increases were specific for SD. bcl-xL, bad and bax had minor and late increases. Cyclin D1 showed a moderately increased expression 72 h after ischemia. A cluster analysis confirmed the related expression patterns of (a) HO-1 and c-myc 24 h after SD, and (b) c-fos and cox-2 early after two-vein occlusion was carried out.