title: Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.
abstract: 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 (180pmoles/2microl) 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.
authors.affiliation: Department of Physiology, CA3145, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, United States.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Glendenning
authors.forename: Tara
authors.initials: T
authors.lastname: Lovekamp-Swan
authors.forename: Derek A
authors.initials: DA
authors.lastname: Schreihofer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D019332:Endothelin-1; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005452:Fluoresceins; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced* / Q000150:complications; D017078:Laser-Doppler Flowmetry / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009930:Organic Chemicals; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013778:Tetrazolium Salts
chemical_list: D019332:Endothelin-1; D004967:Estrogens; D005452:Fluoresceins; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D013778:Tetrazolium Salts; C435731:fluoro jade; C009591:triphenyltetrazolium
references.citation: Neuropharmacology. 2000 Mar 3;39(5):777-87
references.pmid: 10699444
references.citation: Stroke. 1989 Jan;20(1):84-91
references.pmid: 2643202
references.citation: Stroke. 2001 Sep;32(9):2143-8
references.pmid: 11546909
references.citation: Brain Res. 2005 Sep 21;1056(2):158-67
references.pmid: 16125154
references.citation: J Cereb Blood Flow Metab. 1994 Mar;14(2):337-42
references.pmid: 8113329
references.citation: J Neurosci Res. 2006 Feb 15;83(3):469-75
references.pmid: 16397902
references.citation: Cell Mol Neurobiol. 1993 Feb;13(1):15-23
references.pmid: 8458060
references.citation: Neurosci Lett. 1996 Jan 5;202(3):209-13
references.pmid: 8848268
references.citation: Drug Discov Today. 2008 Mar;13(5-6):254-60
references.pmid: 18342802
references.citation: Stroke. 2003 Feb;34(2):338-41
references.pmid: 12574529
references.citation: Exp Neurol. 2006 Oct;201(2):324-34
references.pmid: 16740259
references.citation: Brain Res. 2001 Jan 5;888(1):138-149
references.pmid: 11146060
references.citation: J Cereb Blood Flow Metab. 2006 Sep;26(9):1103-13
references.pmid: 16437060
references.citation: J Neurosci Methods. 1995 Aug;60(1-2):125-31
references.pmid: 8544471
references.citation: Trends Endocrinol Metab. 2003 Jul;14(5):228-35
references.pmid: 12826329
references.citation: Stroke. 1996 Dec;27(12):2282-6
references.pmid: 8969794
references.citation: Neuropathol Appl Neurobiol. 1998 Dec;24(6):487-97
references.pmid: 9888159
references.citation: J Neurosci Methods. 2002 Aug 30;118(2):199-206
references.pmid: 12204310
references.citation: Magn Reson Med. 2001 Oct;46(4):827-30
references.pmid: 11590661
references.citation: Eur J Pharmacol. 2001 Jan 5;411(1-2):71-83
references.pmid: 11137861
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H245-50
references.pmid: 17213481
references.citation: Neuropharmacology. 2004 Jul;47(1):146-55
references.pmid: 15165842
references.citation: J Cereb Blood Flow Metab. 1990 Mar;10(2):290-3
references.pmid: 1689322
references.citation: Life Sci. 2003 Oct 10;73(21):2665-74
references.pmid: 13679235
references.citation: J Cereb Blood Flow Metab. 1993 Sep;13(5):865-71
references.pmid: 8360292
references.citation: Neurosci Lett. 1999 Oct 8;273(3):191-4
references.pmid: 10515191
references.citation: J Neurosci Methods. 2007 May 15;162(1-2):14-8
references.pmid: 17197033
references.citation: J Neurol Sci. 1997 Dec 9;153(1):8-11
references.pmid: 9455971
references.citation: Brain Res. 1995 Mar 27;675(1-2):20-6
references.pmid: 7796130
references.citation: J Neurosci. 1995 Jul;15(7 Pt 2):5372-8
references.pmid: 7623159
references.citation: Brain Res. 2007 Jul 23;1159:54-66
references.pmid: 17582385
references.citation: J Neurocytol. 2000 May-Jun;29(5-6):401-10
references.pmid: 11424956
references.citation: Brain Res. 1999 Oct 2;843(1-2):105-11
references.pmid: 10528116
references.citation: Cephalalgia. 2006 Jan;26(1):33-42
references.pmid: 16396664
references.citation: Neurochem Res. 1999 Dec;24(12):1499-505
references.pmid: 10591398
references.citation: Neurosci Lett. 1995 Feb 6;185(1):65-9
references.pmid: 7731557
references.citation: Behav Brain Res. 2006 Oct 16;173(2):171-80
references.pmid: 16899307
references.citation: Dev Neurosci. 2005 Mar-Aug;27(2-4):112-20
references.pmid: 16046844
references.citation: Neurosci Lett. 2007 Mar 26;415(2):149-53
references.pmid: 17239538
references.citation: Brain Res. 2007 Jun 11;1153:58-67
references.pmid: 17466282
references.citation: Neuroscience. 2006 Aug 11;141(1):27-33
references.pmid: 16690215
references.citation: Hypertension. 2004 Jul;44(1):78-82
references.pmid: 15159380
references.citation: Stroke. 2001 Nov;32(11):2648-57
references.pmid: 11692030
references.citation: Br J Pharmacol. 2003 Sep;140(1):195-201
references.pmid: 12967949