title: The selective oestrogen receptor modulator, LY362321, is not neuroprotective in a rat model of transient focal ischaemia.
abstract: Selective oestrogen receptor modulators (SERMs) may offer improved alternatives to oestrogen as neuroprotectants in experimental stroke. The present study investigated the role of a novel SERM, LY362321, in a rat model of transient middle cerebral artery occlusion (MCAO). Female Sprague-Dawley rats were ovariectomised and began receiving daily s.c. injections of either 1 mg/kg (n = 13), 10 mg/kg (n = 14) of LY362321, or vehicle (n = 13). The left MCA was temporarily occluded (90 min), with cortical blood flow monitoring, at 12 days post ovariectomy. Sensorimotor function was assessed using a neurological score prior to the MCAO and daily for 3 days following the MCAO. Tissue was processed for infarct volume assessment using 2,3,5-triphenyltetra-zolium chloride staining. The results indicated that there were no significant differences amongst groups in cortical blood flow during the MCAO. Furthermore, there was no significant difference in infarct size amongst vehicle, 1, and 10 mg/kg treated animals: 22.9 +/- 5.0, 16.7 +/- 4.2, and 21.1 +/- 4.1, respectively, one-way anova [F(2,32) = 0.542, P = 0.587]. The MCAO induced a significant decline in neurological score in the vehicle group (from 14 to 7 at 24 h post-MCAO) but this was not significantly affected by LY362321 at either dose. In conclusion, pretreatment with a low or high dose of the novel SERM LY362321 did not significantly influence cerebral blood flow, infarct volume, or sensorimotor function in rats exposed to transient 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: T D
authors.initials: TD
authors.lastname: Farr
authors.forename: H V O
authors.initials: HV
authors.lastname: Carswell
authors.forename: D J
authors.initials: DJ
authors.lastname: McCann
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: H U
authors.initials: HU
authors.lastname: Bryant
authors.forename: J A
authors.initials: JA
authors.lastname: Dodge
authors.forename: I M
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D002490:Central Nervous System / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol