title: Estrogen receptor beta agonist diarylpropiolnitrile (DPN) does not mediate neuroprotection in a rat model of permanent focal ischemia.
abstract: Selective estrogen receptor (ER) agonists can indicate which receptor subtypes are implicated in neuroprotection. This study investigated the contribution of ERbeta, using the selective agonist diarylpropiolnitrile (DPN), in a rat model of stroke. Lister Hooded rats were ovariectomized and implanted with mini-pumps containing either DPN (8 mg kg(-1) day(-1)) (n=7) or vehicle (n=5). Sensorimotor function was assessed using a neurological score and the spontaneous forelimb use asymmetry (cylinder) test. One week later the animals received a middle cerebral artery occlusion (MCAO), and T(2)-weighted MRI at 48 h post-MCAO quantified ischemic damage. Functional recovery was tested for 7 days post-MCAO and brains processed for histological verification of infarct size. The MRI images revealed no significant differences in hemispheric lesion volumes between vehicle- and DPN-treated groups (35.6+/-3.5% and 30.8+/-1.7%, respectively [mean+/-SEM]; Student's unpaired t-test df=10, t=-1.357, p=0.453); this was confirmed histologically at 7 days. MCAO induced significant decline in neurological score performance (from 22 to 11 at 2 h post-MCAO) in the vehicle-treated animals, which was not significantly influenced by DPN. MCAO also induced significant changes in forelimb use in the cylinder test (10% reduction in contralateral, 20% reduction in both, and 30% increase in ipsilateral forelimb use) but this response was not significantly different between groups [F(1,1)=2.929, p=0.118, repeated-measures ANOVA]. In conclusion, pretreatment with the ERbeta agonist DPN did not influence infarct size or sensorimotor function in rats exposed to MCAO.
authors.affiliation: Wellcome Surgical Institute and 7T MRI Facility, Division of Clinical Neuroscience, University of Glasgow, Glasgow, UK. Tracy.Farr@nf.mpg.de
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Farr
authors.forename: Hilary V O
authors.initials: HV
authors.lastname: Carswell
authors.forename: Willy
authors.initials: W
authors.lastname: Gsell
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009460:Neurologic Examination; D009570:Nitriles / Q000008:administration & dosage*; D010052:Ovariectomy / Q000379:methods; D011422:Propionates / Q000008:administration & dosage*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D012720:Severity of Illness Index
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D004965:Estrogen Antagonists; D009570:Nitriles; D011422:Propionates