The selective oestrogen receptor modulator, LY362321 is not neuroprotective in a rat model of transient focal ischaemia

T.D. Farr, H.V.O. Carswell, D.J. McCann, M. Sato, H.U. Bryant, J.A. Dodge, I.M. Macrae

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)366-374
Number of pages8
JournalJournal of Neuroendocrinology
Volume20
Issue number3
DOIs
Publication statusPublished - 2008

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Selective Estrogen Receptor Modulators
Middle Cerebral Artery Infarction
Ischemia
Cerebrovascular Circulation
Ovariectomy
Neuroprotective Agents
Sprague Dawley Rats
Chlorides
Estrogens
Stroke
Staining and Labeling
Injections

Keywords

  • stroke
  • oestrogen
  • neuroprotection
  • selective oestrogen receptor modulators
  • pharmacology

Cite this

Farr, T.D. ; Carswell, H.V.O. ; McCann, D.J. ; Sato, M. ; Bryant, H.U. ; Dodge, J.A. ; Macrae, I.M. / The selective oestrogen receptor modulator, LY362321 is not neuroprotective in a rat model of transient focal ischaemia. In: Journal of Neuroendocrinology . 2008 ; Vol. 20, No. 3. pp. 366-374.
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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.",
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The selective oestrogen receptor modulator, LY362321 is not neuroprotective in a rat model of transient focal ischaemia. / Farr, T.D.; Carswell, H.V.O.; McCann, D.J.; Sato, M.; Bryant, H.U.; Dodge, J.A.; Macrae, I.M.

In: Journal of Neuroendocrinology , Vol. 20, No. 3, 2008, p. 366-374.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The selective oestrogen receptor modulator, LY362321 is not neuroprotective in a rat model of transient focal ischaemia

AU - Farr, T.D.

AU - Carswell, H.V.O.

AU - McCann, D.J.

AU - Sato, M.

AU - Bryant, H.U.

AU - Dodge, J.A.

AU - Macrae, I.M.

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AB - 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.

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KW - oestrogen

KW - neuroprotection

KW - selective oestrogen receptor modulators

KW - pharmacology

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