Genes involved in the pathophysiology of perinatal asphyxia

Mechanisms in the pathogenesis of perinatal asphyxia (PA) at the gene level are only beginning to be elucidated, although gene hunting using different ial display has revealed differences in gene expression between hypoxic and normoxic cells in vitro. As no information on gene expression was availabl e from in vivo studies, we decided to use a non-invasive and clinically rel evant animal model of PA for mRNA hunting applying the subtractive hybridiz ation method. mRNAs from normoxic rat brain and brain of rat pups with 20 m in of asphyxia were isolated and compared by this technique. The resulting subtracted mRNAs were converted to cDNA, sequenced and identified by gene b ank data. A series of transcripts representing transcription factors, trans porters, metabolic factors, were found to be up-or downregulated providing insight into mechanisms of PA, and on the other hand, genes with unknown fu nctions could be given a preliminary role i.e, in PA. Results obtained with this powerful tool are now challenging quantitative determination of these genes and gene products at the protein and activity level to confirm their role in PA.