Dexamethasone-induced neuroprotection in hypoxic-ischemic brain injury in newborn rats is partly mediated via Akt activation

• Dex pretreatment significantly reduced the brain injury following HI in newborn rats.
• Wortmannin partially reversed these effects.
• Findings suggest that neuroprotection following Dex against subsequent HI occurs in part via activation of PI3/Akt pathway.

Prior treatment with dexamethasone (Dex) provides neuroprotection against hypoxia ischemia (HI) in newborn rats. Recent studies have shown that the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway plays an important role in the neuroprotection. The objective of this study is to evaluate the role of the PI3K/Akt pathway in the Dex-induced neuroprotection against subsequent HI brain injury. Seven-day-old rat pups had the right carotid artery permanently ligated followed by 160 min of hypoxia (8% oxygen). Rat pups received i.p. injection of either saline or Dex (0.25 mg/kg) at 24 and 4 h before HI exposure. To quantify the effects of a PI3K/Akt inhibitor, wortmannin (1 μl of 1 μg/μl) or vehicle was injected intracerebroventricularly in the right hemisphere on postnatal day 6 at 30 min prior to the first dose of Dex or saline treatment. Dex pretreatment significantly reduced the brain injury following HI which was quantified by the decrease in cleaved caspase-3 protein as well as cleaved caspase-3 and TUNEL positive cells at 24 h and percent loss of ipsilateral hemisphere weight at 22 d after HI, while wortmannin partially reversed these effects. We conclude that Dex provides robust neuroprotection against subsequent HI in newborn rats in part via activation of PI3/Akt pathway.