Temporal and spatial gene expression patterns after experimental stroke in a rat model and characterization of PC4, a potential regulator of transcription.
We have used the middle cerebral artery occlusion model in the rat in combination with microarray transcript imaging to study changes in gene activity after ischemic stroke. We analyze transcriptional changes in three regions of the affected, ipsilateral brain sphere using contralateral tissues from the same animal as a control over several time points in 180 individual RNA samples. After 1 h transcription factors and signaling molecules are expressed in all tissues followed by the induction of tissue repair-related genes in the cortices which undergo regeneration. Some of these genes are turned on by PC4, which is upregulated in tissues surrounding the infarct core. Interestingly, PC4 is a nerve growth factor (NGF)-inducible gene and has been associated in earlier studies with neuronal growth processes. The expression mode of PC4, the cellular localization of the gene product, and the functional properties of downstream genes induced in vivo and in vitro using transgenic cell lines suggest that PC4 is a regulator of transcription involved in tissue regeneration after ischemic stroke. The novel experimental strategy applied here is suited to provide insight into the molecular mechanisms underlying stroke and tissue regeneration and may enable the discovery of preventive medicines.
Roth
Adrian
A
Roche Center for Medical Genomics, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Gill
Ramanjit
R
Certa
Ulrich
U
D000818:Animals; D000906:Antibodies; D001921:Brain / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D015533:Transcriptional Activation / Q000502:physiology*
D000906:Antibodies; C084979:Ifrd1 protein, rat; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger