title: Dexamethasone-induced neuroprotection in hypoxic-ischemic brain injury in newborn rats is partly mediated via Akt activation.
abstract: 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 160min of hypoxia (8% oxygen). Rat pups received i.p. injection of either saline or Dex (0.25mg/kg) at 24 and 4h before HI exposure. To quantify the effects of a PI3K/Akt inhibitor, wortmannin (1μl of 1μg/μl) or vehicle was injected intracerebroventricularly in the right hemisphere on postnatal day 6 at 30min 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 24h and percent loss of ipsilateral hemisphere weight at 22d 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.
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Yangzheng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Emergency, The First affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Junming
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Office of Health Data and Research, Mississippi State Department of Health, Jackson, MS 39216, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA. Electronic address: abhatt@umc.edu.
authors.forename: Abhay J
authors.initials: AJ
authors.lastname: Bhatt
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002339:Carotid Arteries; D053148:Caspase 3 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D053148:Caspase 3; D003907:Dexamethasone; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C505410:Casp3 protein, rat
keywords: Akt; Apoptosis; Glucocorticoid; Hypoxia-ischemia; Newborn; Stroke