title: The neuroprotective effect of 17β-estradiol is independent of its antioxidative properties.
abstract: 17β-Estradiol (E2) is neuroprotective in experimental models of stroke. While some postulate a mainly antioxidative action due to E2׳s free C3 hydroxyl group at its A-ring, others suggest that neuroprotection is mediated by a hormonal, receptor mediated effect. The aim of the current study was to clarify this issue by testing whether E2 analogues lacking hormonal activity are also neuroprotective following cerebral ischemia.
  
  
  
  Focal cerebral ischemia was induced in male C57/BL6 mice by laser-Doppler-controlled endovascular occlusion of the middle cerebral artery for 40min. Mice received either 1) memantine, a NMDA-receptor antagonist, as a positive control, 2) E2 (1400µg/kg b.w.), or 3) 2,4,6-trimethylphenol (TMP), an E2 analogue without hormonal activity (1400, 140, or 14µg/kg b.w.). Motor function was tested 3h and 24h after ischemia. Thereafter mice were sacrificed and brain damage was quantified by histomorphometry.
  
  
  
  Treatment with memantine or E2 significantly reduced infarct volume by >40% and significantly improved neurological function while treatment with TMP had no effect.
  
  
  
  E2 is equally neuroprotective as antagonization of NMDA receptors while E2 analogues without hormonal activity are not neuroprotective. Therefore the current data suggest that the neuroprotection activity of E2 is independent of its free-radical scavenging properties.
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Munich Medical Center, Ludwig-Maximilians-University Munich, Germany; Institute for Surgical Research, University of Munich Medical Center, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Gröger
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Ludwig-Maximilians-University Munich, Germany; Institute for Stroke and Dementia Research, University of Munich Medical Center, Ludwig-Maximilians-University Munich, Germany. Electronic address: nikolaus.plesnila@med.uni-muenchen.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000473:pathology; D003408:Cresols / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D003408:Cresols; D006728:Hormones; D018696:Neuroprotective Agents; D004958:Estradiol; C505148:2,4,6-trimethylphenol; D008559:Memantine
keywords: 17β-estradiol; Antioxidation; Hormone; Neuroprotection; Phenol; Stroke