Dose dependence and therapeutic window for the neuroprotective effects of 17beta-estradiol when administered after cerebral ischemia.
The present study was undertaken to determine if the neuroprotective effect of 17beta-estradiol (E(2)) when administrated after ischemia is dose-dependent and if the therapeutic window for estrogen can be prolonged. Ischemic injury was induced by permanent middle cerebral artery occlusion (p-MCAO). Administration of E(2) at 30 min after ischemia resulted in a reduction in lesion volume. A higher dose of E(2) extended the therapeutic window to 6h after cerebral ischemia in 33% of the rats. These findings suggest that postischemic treatment with estrogen affords protection against ischemic damage and that it acts within a clinically useful therapeutic window.
Liu
Ran
R
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
Wang
Xiaofei
X
Liu
Qing
Q
Yang
Shao-Hua
SH
Simpkins
James W
JW
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D004958:Estradiol