TY - JOUR
T1 - Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats
AU - Glendenning, Michele L.
AU - Lovekamp-Swan, Tara
AU - Schreihofer, Derek A.
N1 - Funding Information:
This work was supported by NIH R01 AT001882 to D.A.S. The authors thank Drs. Ann Schreihofer and Adviye Ergul for helpful comments on this manuscript.
PY - 2008/11/14
Y1 - 2008/11/14
N2 - 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.
AB - 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.
KW - Endothelin
KW - Estrogen
KW - Experimental stroke
KW - Middle cerebral artery occlusion
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=53249132540&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2008.09.006
DO - 10.1016/j.neulet.2008.09.006
M3 - Article
C2 - 18790008
AN - SCOPUS:53249132540
SN - 0304-3940
VL - 445
SP - 188
EP - 192
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -