Changes in gene regulation and protein activation following acute ischaemic stroke in a rat middle cerebral artery occlusion model

Saka, Mohamad, Gaffney, John, Kumar, Patricia, Kumar, Shant and Slevin, Mark (2005) Changes in gene regulation and protein activation following acute ischaemic stroke in a rat middle cerebral artery occlusion model. [Conference or Workshop Item] (Unpublished)

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Abstract

Ischaemic stroke is a leading cause of death and disability worldwide. Usually it results from a transient or permanent reduction in cerebral blood flow. 2/3 of patients survive but are left with significant degrees of sensorimotor, cognitive, or other impairment. Previous studies have described the importance of individual proteins on infarct development and tissue regeneration after stroke. Here we have performed a global study employing a cDNA microarray (containing 1200 genes) to examine gene expression 1 h–21 days after Middle Cerebral Artery Occlusion (MCAO) in a rat model. Tissue samples from infarct, penumbra (the region of tissue surrounding the ischaemic core) and normal contralateral hemisphere were examined. The number of genes up-regulated greater than 2 fold increased up to 3 days (350 genes) decreasing again by 21 days (30 genes), while the down-regulated genes were increased up to 21 days (85 genes). We have used semi-quantitative RT-PCR to confirm differences in regulation of novel genes encoding Inflammatory (IL-7 and CD24), apoptotic (Cathepsin-L and C-erbA-b), neuroprotective/anti-apoptotic (BTG-2, ERK-3, LIF/DIF), and signalling intermediates (c-ets-1) in the stroke hemisphere. Confirmation of changes in expression of key genes was made using western blotting. Identification of novel gene/protein de-regulation might improve our understanding of the pathophysiology of stroke and lead to identification of new therapeutic targets.