Focal brain infarcts are surrounded by extended perilesional zones that comprise 
the partially ischemic penumbra but also completely non-ischemic cortex of the 
remote ipsilateral hemisphere. To delineate the impact of lesion-associated vs. 
remote processes on transcriptional programming after focal ischemia, we used 
cDNA array analysis, quantitative real-time polymerase chain reaction and 
immunohistochemistry in the photothrombosis model of circumscribed cortical 
ischemia in rats. At an early stage of 4 h after ischemia, gene induction 
occurred to a similar extent in the ischemic infarct and remote non-ischemic 
cortex of the ipsilateral hemisphere. Among the genes induced in non-ischemic 
cortex we found the NGF-inducible genes PC3, VGF and Arc, the transcriptional 
regulators I kappa B-alpha and Stat3, and the beta-chemokine MIP-1 alpha (CCL3). 
At 3 days, the spatial pattern of gene expression had changed dramatically with 
brain fatty acid-binding protein as the only gene significantly induced in 
non-ischemic ipsilateral cortex. In contrast, numerous genes were exclusively 
regulated at the lesion site, comprising genes involved in cell cycle 
regulation, proteolysis, apoptosis, lipid homeostasis and anti-inflammatory 
counter-regulation. Cortical spreading depression was identified as the main 
mechanism underlying gene induction in remote non-ischemic cortex. Our data 
demonstrate a dynamic spatiotemporal pattern of gene induction, which may 
contribute to delayed progression of damage or, alternatively, mediate 
neuroprotection, tissue remodeling and functional compensation.