Expression of c-FOS and c-JUN proteins in the progression of brain damage

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1.Using a hypoxic-ischemic brain damage model of neonatal rats, we gave rats two kinds of insult : a 90-min consecutive insult and repeated intermittent exposure for 10 minutes with 10 minute intervals, for a total of 90 minutes of exposure in 180 minutes while observing them for hypoxic-ischemic stress. First, we investigated the change in cerebral blood flow and nitric oxide (NO) during hypoxic-ischemic insult. NO was generated as cerebral blood flow decreased during the insult ; however, even after cerebral blood flow returned to control level during a break period, NO was still generated. The generation of NO increased again after the insult ended, suggesting some relationship to the occurrence of brain damage.2.The generation of inducible nitric oxide synthase (iNOS) and peroxynitrite caused by hypoxic-ischemic insult was examined. In addition, after the administration of S-methyl-isothiourea (SMT), a selective inhibitor of iNOS, we observed the degree of brain damage and the expression of 3-nitotyrosine (NT), an index of the generation of peroxynitrite. The expression of and iNOS proteins was observed 6-36 hours and 12-48 hours after the start of the insult, respectively. NT expressed mostly on the side of ischemia and reached its maximum 48 hours. On the other hand, with the administration of SMT, brain tissue damage decreased significantly, and the expression of NT was restrained.3.After the first insult., second insults were given at various intervals. As a result, second insults given while iNOS activity increased worsened brain damage. On the other hand, the expansion of the disorders was restrained by the administration of the iNOS inhibitor. These results suggested that, in the perinatal immature brain, the expression of iNOS caused by hypoxic-ischemic insult and increased production of peroxynitrite is related to the worsening of brain damage.