Cooperative Expression of Survival p-ERK and p-Akt Signals in Rat Brain Neurons After Transient MCAO

Brain Res. 2003 Feb 7;962(1-2):21-6. doi: 10.1016/s0006-8993(02)03774-5.


In order to determine possible coordinate expression of major survival signals, immunofluorescent analyses for phosphorylated ERK (p-ERK) and phosphorylated Akt (p-Akt) were carried out after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. p-Akt single positive cells (E-/A+) were found in the sham control brains with weak signal intensity. The levels of both survival signals concurrently increased from 1 to 3 h after the reperfusion with the peak at 1 h, and the signals were much stronger in the ischemic penumbra (IP) than ischemic core (IC). The number of E-/A+ cells was larger in both the IC and IP than that of p-ERK single positive cells (E+/A-). The E+/A- cells were primarily expressed at 1 h in the IP. The number of p-ERK plus p-Akt double positive cells (E+/A+) peaked at 1 h, and the intensity was much stronger in the IP than IC. These findings suggest that p-ERK and p-Akt play independent roles, respectively as emergency or maintenance signal for survival at an early stage after reperfusion, and that both signals were cooperatively expressed especially in the IP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology*
  • Fluorescent Antibody Technique
  • Ischemic Attack, Transient / enzymology*
  • Male
  • Middle Cerebral Artery
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / enzymology*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Wistar


  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases