A microarray study of gene expression in human brain after ischaemic stroke: identification of novel genes and comparison with the rat middle cerebral artery occlusion model of ischaemic stroke

Mitsios, Nicholas, Saka, Mohamad, Gaffney, John, Kumar, Patricia, Kumar, Shant and Slevin, Mark (2005) A microarray study of gene expression in human brain after ischaemic stroke: identification of novel genes and comparison with the rat middle cerebral artery occlusion model of ischaemic stroke. [Conference or Workshop Item] (Unpublished)

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Abstract

Recent therapeutic trials of novel proteins identified as potentially neuroprotective in animal models of ischaemic stroke have failed perhaps due to the presence of undefined differences in gene/protein regulation which exist between these models and stroke in man. Material and methods: In this study, cDNA micro-array technology was used to screen for changes in gene expression in pooled brain tissue (n = 3) from patients who died 2–6 (Early – E), 9–17 (Medium – M) and 26–37 (Late – L)days after acute large vessel ischaemic stroke. Western blotting was used to study protein expression in individual patients and immunohistochemistry to localize the cellular expression of these proteins. Results: In the first group (E), 98 genes were upregulated and 7 downregulated in stroke-affected tissue, as compared to normal contralateral tissue. In the second group (M), 87 genes were upregulated and 13 downregulated, and in the third group (L), there was an increase in the expression of 33 genes and a decrease in the expression of only 1. Differential expression of novel genes was confirmed by semi-quantitative RT-PCR, and included the pro-inflammatory genes High Mobility Group Protein 1 (HMG1), CD53 and Inhibitor of Neuronal NO Synthase (PIN), the pro-apoptotic genes Inhibitor of Differentiation 2 (Id2), Integrase Interactor 1 (Ini1) and Cathepsin L and the anti-apoptotic genes Prion Protein (PrP), Ribosomal S3a and P21 Activated Kinase 1 (Pak1). Conclusion: Besides identifying novel genes related to stroke, comparison of these results with a rat middle cerebral artery occlusion model of ischaemic stroke demonstrated important similarities and differences.