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[Background]: Altered gene expression is an important feature of ischemic cerebral injury and
affects proteins of many functional classes. We have used microarrays to investigate the changes in
gene expression at various times after middle cerebral artery occlusion in human and rat brain.
[Results]: Our results demonstrated a significant difference in the number of genes affected and the
time-course of expression between the two cases. The total number of deregulated genes in the
rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets,
184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both
cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel
genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and
integrase interactor 1, was further analyzed by RT-PCR, Western blotting and
immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11.
[Conclusion]: Our findings confirmed previous studies reporting that gene expression screening
can detect known and unknown transcriptional features of stroke and highlight the importance of
research using human brain tissue in the search for novel therapeutic agents.
This work was supported by the Higher Education Funding Council for England (HEFCE) and the Research Institute for Health and Social Change
(RIHSC).
Peer reviewed