Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary: To investigate the adaptive mechanisms fol lowing carotid artery ligation in immature rats, histologic injury and tissue levels of ATP were compared after ex posure to identical episodes of hypoxia induced either 3 or 24 h postligation. Histologic injury, assessed in both 9-day-and 23-day-postnatal animals after survival for ) week, was markedly diminished in animals exposed to hypoxia 24 h postligation compared to that in animals exposed to hypoxia 3 h postligation. In 9-day-postnatal animals, ATP levels in the cerebral cortex ipsilateral to Unilateral carotid artery ligation followed by ex posure to systemic hypoxia is a model that has been widely used to investigate hypoxia-ischemia in the brain of immature rats (Rice et aI. , 198 1; Welsh et aI. , 1982;Silverstein and Johnston, 1984; Dwyer et aI. , 1987; McDonald et aI. , 1987; Andine et ai. , 1988; Ferreiro et ai. , 1990; Barks et ai. , 199 1; Blu menfeld et ai. , 1992; Gubits et ai. , 1993; Nozaki et ai. , 1993). Typically, 10-12 rat pups (one litter) un dergo sequential carotid artery ligation followed by simultaneous exposure to hypoxia. As a result, the interval between ligation and onset of hypoxia may 1137the ligation were depleted during hypoxia to 0.39 ± 0.49 mmol/kg (mean ± SD; N = 15) in animals exposed to hypoxia 3 h postligation but were maintained at 2.04 ± 0.26 mmollg (N = 18; p < 0.001) in animals exposed to hypoxia 24 h postligation. Thus, preservation of ATP may account for the diminution of cellular injury that results from delaying the onset of hypoxia from 3 to 24 h after carotid artery ligation in immature rats. METHODS Preparation of the animalsSprague-Dawley rats, 9 and 23 days postnatal, were anesthetized with a mixture of 2% halothane, 50% O2, balance N2• Through a neck incision, the common carotid artery on the left side was isolated, doubly ligated with

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