Estrogen receptor beta agonist diarylpropiolnitrile (DPN) does not mediate neuroprotection in a rat model of permanent focal ischemia.
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.
Farr
Tracy D
TD
Wellcome Surgical Institute and 7T MRI Facility, Division of Clinical Neuroscience, University of Glasgow, Glasgow, UK. Tracy.Farr@nf.mpg.de
Carswell
Hilary V O
HV
Gsell
Willy
W
Macrae
I Mhairi
IM
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
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D004965:Estrogen Antagonists; D009570:Nitriles; D011422:Propionates