Early and delayed induction of immediate early gene expression in a novel focal cerebral ischemia model in the rat

This study aimed at evaluating changes in expression of immediate early gen es in a new photothrombotic focal ischemia model that exhibits late spontan eous reperfusion and morphological restoration in the region-at-risk within the cerebral cortex. Gene expression was studied with Northern blots, in s itu hybridization and immunohistochemistry. At early time points (1-4 h), n erve growth factor-induced gene A and B, and c-fos mRNAs, were quickly indu ced throughout the ipsilateral cortex, with no obvious differences between the region-at-risk and remote cortical areas. High concentrations of nerve growth factor-induced gene A and c-Fos proteins were present within the reg ion-at-risk even when cortical cerebral blood flow was as low as 40% of con trol values. At 4 h the nerve growth factor-induced gene A mRNA and protein expression was significantly decreased in the hippocampus vs. naive contro ls. However, a small decrease was also found in sham-operated and anaesthet ized controls. A late induction, at 5 days, of c-fos and nerve growth facto r-induced gene B mRNAs was seen bilaterally in the hippocampus and also, in the case of nerve growth factor induced-gene B, in the contralateral corte x. A complex pattern of changes in immediate early gene expression occurs a fter reversible focal cortical ischemia. This may be important for tissue r ecovery as well as neuropsychiatric symptoms after stroke.