Related Experiment Videos
LY353381.HCl, a selective estrogen receptor modulator, and experimental stroke
M I Rossberg1, S J Murphy, R J Traystman
1Departments of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stroke
|January 11, 2000
Summary
A selective estrogen receptor modulator, LY353381.HCl (LY), reduced stroke-induced brain damage in ovariectomized rats. This neuroprotection in the caudoputamen was observed without altering cerebral blood flow, suggesting a novel therapeutic mechanism for stroke treatment.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Estrogen replacement therapy's role in stroke prevention is debated.
- Estrogen deficiency after ovariectomy diminishes neuroprotection against stroke.
- 17β-estradiol offers protection within a narrow, suboptimal therapeutic range.
Purpose of the Study:
- To investigate if LY353381.HCl (LY), a selective estrogen receptor modulator, reduces tissue infarction after middle cerebral artery (MCA) occlusion in estrogen-deficient rats.
- To test the neuroprotective potential of LY in a model of focal cerebral ischemia.
Main Methods:
- Ovariectomized female rats received LY or vehicle via gavage.
- Middle cerebral artery (MCA) occlusion was induced for 2 hours, followed by 22 hours of recovery.
- Infarction volumes were quantified using TTC staining; regional cerebral blood flow (CBF) was measured using autoradiography.
Main Results:
- LY treatment significantly reduced caudoputamen infarction compared to vehicle (49% vs. 64%).
- No significant difference in cerebral cortical infarction was observed between groups.
- LY did not alter end-ischemic CBF or blood flow distribution within the MCA territory.
Conclusions:
- LY confers neuroprotection against focal cerebral ischemia in the caudoputamen of ovariectomized female rats.
- The neuroprotective mechanism of LY is independent of preserving ischemic cerebral blood flow.