title: Impact of estrogen receptor beta activation on functional recovery after experimental stroke.
abstract: Acute treatment with 17β-estradiol provides effective neuroprotection during the first days after acute brain injury, however, effects of chronic activation of estrogen receptor beta (ERβ) on recovery of function after experimental stroke have not been investigated. The present study, therefore, was conducted to test if delayed treatment with the specific ERβ ligand 4-(1-phenyl-cyclohexyl)-phenol (AC-131) improves recovery of lost neurological function after permanent focal stroke induced by photothrombosis in adult Sprague-Dawley rats. Treatment was initiated on day 2 after photothrombosis and AC-131 (1, 10, and 50 mg/kg) was administered by daily subcutaneous injections for 14 days. On day 2, 4, 6, 8, 11, 14, and 17 after photothrombosis, functional deficits were assessed by the paw placement test, a standardized grip strength test and an adhesive removal test. Daily treatment with AC-131 significantly improved test scores in all three behavioral tests. Importantly, improved function was not associated with a decrease in infarct volume on day 17 after stroke onset. Our results suggest that increased activity of the ERβ is involved in mechanisms of stroke recovery.
authors.affiliation: Department of Clinical Sciences, Division of Neurosurgery, Laboratory for Experimental Brain Research, Lund University, BMC A13, Lund S-22184, Sweden.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Madinier
authors.affiliation: Department of Clinical Sciences, Division of Neurosurgery, Laboratory for Experimental Brain Research, Lund University, BMC A13, Lund S-22184, Sweden.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Wieloch
authors.affiliation: Chemical Biology & Therapeutics, Department of Experimental Medical Science, Lund University, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Olsson
authors.affiliation: Department of Clinical Sciences, Division of Neurosurgery, Laboratory for Experimental Brain Research, Lund University, BMC A13, Lund S-22184, Sweden. Electronic address: karsten.ruscher@med.lu.se.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D020767:Intracranial Thrombosis / Q000150:complications; D008297:Male; D053580:Muscle Strength / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology*; D013997:Time Factors
chemical_list: C000592026:4-(1-phenylcyclohexyl)phenol; D003510:Cyclohexanes; D020847:Estrogen Receptor Modulators; D047629:Estrogen Receptor beta; D010636:Phenols
keywords: AC-131; Cerebral ischemia; Estrogen receptor beta; Hormone therapy; Photothrombosis; Stroke recovery