Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

• Published in: Neuroscience letters 2008-11, Vol.445 (2), p.188-192
• Main Authors: Glendenning, Michele L., Lovekamp-Swan, Tara, Schreihofer, Derek A.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain Infarction - etiology; Brain Infarction - prevention & control; Disease Models, Animal; Endothelin; Endothelin-1; Estrogen; Estrogens - therapeutic use; Experimental stroke; Female; Fluoresceins; Fundamental and applied biological sciences. Psychology; Infarction, Middle Cerebral Artery - chemically induced; Infarction, Middle Cerebral Artery - complications; Laser-Doppler Flowmetry - methods; Medical sciences; Middle cerebral artery occlusion; Motor Activity - drug effects; Neurology; Neuroprotection; Neuroprotective Agents - therapeutic use; Organic Chemicals; Ovariectomy - methods; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Tetrazolium Salts; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.09.006

Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague–Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180 pmoles/2 μl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.