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Vol. 77, No. 1, 2003
Issue release date: January 2003
Section title: Reproductive Neuroendocrinology
Neuroendocrinology 2003;77:44–50
(DOI:10.1159/000068332)

Tamoxifen, a Selective Estrogen Receptor Modulator, Reduces Ischemic Damage Caused by Middle Cerebral Artery Occlusion in the Ovariectomized Female Rat

Mehta S.H. · Dhandapani K.M. · De Sevilla L.M. · Webb R.C. · Mahesh V.B. · Brann D.W.
aDepartment of Physiology, and bInstitute of Molecular Medicine and Genetics, Neurobiology Program, and Department of Neurology, Medical College of Georgia, Augusta, Ga., USA

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Article / Publication Details

First-Page Preview
Abstract of Reproductive Neuroendocrinology

Received: 5/13/2002
Accepted: 11/5/2002
Published online: 3/10/2003

Number of Print Pages: 7
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

Previous work has demonstrated that physiological concentrations of 17β-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, can similarly protect the female rat brain against ischemic stroke damage. Adult female rats were bilaterally ovariectomized and implanted subcutaneously with either a placebo or tamoxifen time-release pellet (0.1, 0.8 or 2.4 mg/kg/day). One week later, the animals underwent permanent MCAO to assess the protective ability of the different tamoxifen doses on brain infarct size. As expected, MCAO produced a large infarct (∼53%) of the affected cerebral hemisphere in placebo (control) animals. The 0.1 mg/kg/day dose of tamoxifen did not exhibit any significant protective effects, however; the 0.8 and 2.4 mg/kg/day doses of tamoxifen, which are in the therapeutic range, dramatically reduced infarct of the affected cerebral hemisphere (∼70% reduction) as compared to the controls. The reduction of infarct size was primarily due to protection of two major structures, the cerebral cortex and striatum. Laser Doppler analysis further revealed that tamoxifen had no significant effect on cerebral blood flow either before or after MCAO, suggesting that tamoxifen protection is independent of cerebral blood flow changes. Further studies showed that tamoxifen pellets implanted at the time of MCAO did not reduce infarct size, suggesting that pretreatment with tamoxifen is necessary to observe a protective effect. These studies suggest that clinically important SERMs may have an additional unrecognized beneficial effect of protection of the female brain.


  

Author Contacts

Dr. Darrell W. Brann
Institute of Molecular Medicine and Genetics, Neurobiology Program
1120 15th Street, Medical College of Georgia
Augusta, GA 30912 (USA)
Tel. +1 706 721 7779, Fax +1 706 721 8685, E-Mail dbrann@mail.mcg.edu

  

Article Information

Received: May 13, 2002
Accepted after revision: November 5, 2002
Number of Print Pages : 7
Number of Figures : 6, Number of Tables : 0, Number of References : 38

  

Publication Details

Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Founded 1965 by E. Bajusz. Continued by K.M. Knigge (1973–1978), W.F. Ganong (1979–1984), S.M. McCann (1985–1993)

Vol. 77, No. 1, Year 2003 (Cover Date: January 2003)

Journal Editor: C. Kordon, Paris
ISSN: 0028–3835 (print), 1423–0194 (Online)

For additional information: http://www.karger.com/journals/nen


Article / Publication Details

First-Page Preview
Abstract of Reproductive Neuroendocrinology

Received: 5/13/2002
Accepted: 11/5/2002
Published online: 3/10/2003

Number of Print Pages: 7
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


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