title: Contribution of estrogen receptors alpha and beta in the brain response to traumatic brain injury.
abstract: OBJECTIVE
  Although there is evidence that estradiol has neuroprotective effects after traumatic brain injury (TBI) in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. The authors therefore examined the roles of the different ERs in this effect. Here the authors used the ERα selective agonist propyl pyrazole triol (PPT) and the ERβ selective agonist diarylpropionitrile (DPN) alone and in combination in female rats to investigate this question.
  
  
  METHODS
  Before the ovariectomized animals were injured using the Marmarou TBI technique, they were randomly divided into the following 9 groups: control, sham, TBI, vehicle, E1 (physiological dose of 17-β estradiol), E2 (pharmacological dose of 17-β estradiol), PPT, DPN, and PPT+DPN. Levels of blood-brain barrier (BBB) disruption (5 hours) and water content (24 hours) were evaluated after TBI. In groups receiving drugs or vehicle, treatment was administered as a single dose intraperitoneally 30 minutes after induction of TBI.
  
  
  RESULTS
  Results showed that brain edema or brain water content after TBI was lower (p < 0.001) in the E2, PPT, DPN, and PPT+DPN groups than it was in the vehicle group. After trauma, the Evans blue dye content or BBB permeability was significantly higher in the TBI and vehicle groups (p < 0.001) than in the E2, PPT, DPN, and PPT+DPN groups. The inhibitory effects of PPT+DPN on brain water content, neurological scores, and Evans blue dye content were the highest for all groups. Although both PPT and DPN increased neurological scores after TBI, PPT appears to be more effective in increasing neurological scores.
  
  
  CONCLUSIONS
  Neuroprotective effects of estradiol on brain edema, BBB permeability, and neurological scores are mediated through both ERα and ERβ. This may suggest a therapeutic potential in the brain trauma for ER-specific agonists.
authors.affiliation: Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran.
authors.forename: Saleh Zahedi
authors.initials: SZ
authors.lastname: Asl
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khaksari
authors.forename: Ali Siahposht
authors.initials: AS
authors.lastname: Khachki
authors.forename: Nader
authors.initials: N
authors.lastname: Shahrokhi
authors.forename: Shahla
authors.initials: S
authors.lastname: Nourizade
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001834:Body Water; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism*; D005260:Female; D018696:Neuroprotective Agents / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018696:Neuroprotective Agents; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol