Cerebral expression of DNA repair protein, Ku70, and its association with cell proliferation following cerebral hypoxia-ischemia in neonatal rats.

We hypothesized that increased Ku70 expression could be involved in recovery following cerebral hypoxia-ischemia. We investigated the progression of cerebral alterations in Ku70 expression at different time points (24 h, 72 h, 1 week, 4 weeks and 8 weeks) after hypoxia-ischemia (right carotid artery occlusion plus 1.5h of hypoxia) in neonatal rats. To determine whether in addition to its known role of DNA repair, Ku70 was associated with cell death or cell proliferation we performed double staining for Ku70 and DNA fragmentation or bromodeoxyuridine, respectively. The results show that Ku70 expression was increased in the infarct core and peri-infarct regions at 24h following hypoxia-ischemia. The increased Ku70 expression was transient in the infarct core with a loss of Ku70 positive cells over days. In contrast, in the peri-infarct region the expression of Ku70 remained increased at chronic times 8 weeks following the insult. Cells positive for DNA fragmentation were not co-localized with cells positive for Ku70 after an insult. However, most of the cells positive for bromodeoxyuridine indicative of cell proliferation were positive for Ku70 in the peri-infarct region at 8 weeks after the insult. Considering the roles of Ku70 in DNA repair or inhibiting apoptosis and its co-localization within cells that had undergone proliferation, Ku70 may be considered a potential novel target to enhance recovery following hypoxia-ischemia.

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