17beta-estradiol attenuates programmed cell death in cortical pericontusional zone following traumatic brain injury via upregulation of ERalpha and inhibition of caspase-3 activation

Neurochem Int. 2011 Jan;58(1):126-33. doi: 10.1016/j.neuint.2010.11.006. Epub 2010 Nov 17.

Abstract

Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of pharmacological intervention. It is well studied that 17beta-estradiol has a protective role in ischemic brain injury, but its role in brain protection of traumatic brain damage deserves further investigation, especially in pericontusional zone. Here we show that 17beta-estradiol enhances the protein expression and mRNA induction of estrogen alpha receptor (ERalpha) and prevents from programmed cell death in cortical pericontusional zone. ERalpha specific antagonist blocks this protective effect of 17beta-estradiol. Caspase-3 activation occurs in cortical pericontusional zone of the oil-treated injured rat brain and its activation is inhibited by 17beta-estradiol treatment. Additionally, ERalpha specific antagonist reverses this inhibition. Pan-caspase inhibitor also protect cortical pericontusional zone from programmed cell death. Our present study indicates 17beta-estradiol protects from programmed cell death in cortical pericontusional zone via enhancement of ERalpha and decrease of caspase-3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Brain Injuries / pathology*
  • Caspase Inhibitors*
  • Cerebral Cortex / pathology*
  • Enzyme Activation / drug effects
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / biosynthesis*
  • Female
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Oligopeptides / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects

Substances

  • Caspase Inhibitors
  • Estrogen Receptor alpha
  • Oligopeptides
  • RNA, Messenger
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • Estradiol