LOCALIZATION OF C-FOS, C-JUN, AND HSP70 MESSENGER-RNA EXPRESSION IN BRAIN AFTER NEONATAL HYPOXIA-ISCHEMIA

The sites of expression of early response mRNAs were determined in the brains of 7-day-old rat pups exposed to unilateral carotid artery lig ation followed by 3 h of hypoxia. Pups were sacrificed after recovery periods ranging from 10 min to 24 h. In agreement with our previous no rthern blot analysis18, in situ hybridization of coronal brain section s to probes for c-fos, c-jun, and heat-inducible hsp70 revealed a mark ed induction and subsequent disappearance of all three mRNAs during th is time period. We observed co-localization of the 2 immediate early g ene (IEG) mRNAs, c-fos and c-jun, which encode proteins that act in co mbination to regulate subsequent gene expression. These mRNAs were exp ressed in all regions known to be vulnerable to permanent injury in th is model, such as the cortex, hippocampus, and striatum, as well as in other regions that are spared from permanent damage, such as contrala teral cortex and lateral ventricular neuroepithelium. The temporal and regional co-localization of c-fos and c-jun suggests that the transcr iptional regulatory activity of their protein products could play a ro le in plasticity associated with death or recovery from injury in the immature brain. Hsp70 mRNA expression was induced in nearly all of the animals that were positive for IEG mRNAs. Although the most frequent site of expression for all three mRNAs was the ipsilateral cerebral co rtex, hsp70 expression was restricted to the ipsilateral hemisphere an d absent from a number of structures that were positive for c-fos and c-jun. In addition, the patterns of expression of hsp70 within specifi c structures frequently differed from those of the IEGs, implying that although both cellular early response systems are activated in this m odel, their specific functions are carried out within different microe nvironments.