[The regulation of Akt signaling on axonal density after hypoxic-ischemic brain injury in neonatal rat]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Mar;44(2):274-9.
[Article in Chinese]


Objective: To investigate the activity of protein kinase B (Akt) and its downstream protein, glycogen synthase kinase-3beta (GSK-3beta) under hypoxia-ischemia (HI), and the possible regulation for axonal density.

Methods: Postnatal day 10 SD rats were suffered the right common carotid artery ligation and 8% mixture of oxygen and nitrogen hypoxia 2.5 h to produce HI model. The expression of total and phosphorylated Akt and GSK-3beta was detected by western blot after HI. After pretreatment of Akt inhibitor, wortmannin or LY294002, Western blot detect the expression of total and phosphorylated of Akt, GSK-3beta at 4 h and 24 h after HI. After pretreatment of wortmannin, axonal density was determined by Bielschowsky silver impregnation, and histological injury was evaluated by hematoxylin and eosin (HE) staining.

Results: The expression of total Akt and GSK-3beta remained unchanged after HI. p-Akt protein significantly decreased at 0.5 h, increased at 2 h and reached the highest at 4 h, returned to baseline at 8 h, declined at 24 and 48 h after HI, and finally returned to baseline again at 72 h compared with that of sham controls, p-GSK-3beta protein decreased at 0. 5 h, increased at 2 h, reached the highest at 4 h, returned to baseline at 8 and decreased at 24 h, reached the lowest at 48 h, and returned to baseline at 72 h. Wortmannin or LY294002 intervention didn't change the expression of total Akt and GSK-3beta, while decrease the p-Akt and p-GSK-3beta expression. HI cause decreased axonal density, and the histological injury of brain. Wortmannin pretreatment could aggravate the histological injury and decrease axonal density after HI.

Conclusion: The Akt pathway is involved in axonal density and histological brain injury after HI in neonatal rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Animals, Newborn
  • Axons / pathology*
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hypoxia-Ischemia, Brain / pathology*
  • Male
  • Morpholines / pharmacology
  • Proto-Oncogene Proteins c-akt / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Wortmannin


  • Androstadienes
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Wortmannin