Estrogen is protective against tissue damage and neurological deficit after experimental cerebral ischemia. Although the precise mechanisms are unknown, estrogen's beneficial properties are in part linked to rapid activation of signal transduction pathways that lead to the transcription of neuroprotective genes. Signal transducer and activator of transcription 3 (STATS) is a transcription factor that is activated in response to both estrogen and ischemia, and is known to bind and stimulate the transcription of neuroprotective genes, such as bcl-2 and bcl-xL. We propose to test the overall hypothesis that estrogen's neuroprotective effects in cerebral ischemia are mediated, in part, via STATS. We will inhibit STATS activation to determine its role in mediating the effect of estradiol to reduce infarct size after middle cerebral artery occlusion (MCAO) in ovariectomized female rats. We will use Western blotting to determine the effect of estradiol on STATS phosphorylation and nuclear translocation. Finally, we will use quantitative real-time PCR and electrophoretic mobility shift assay (EMSA) to determine the effect of estradiol on bcl-2 and bcl-xL gene expression and potential STAT-3 binding to their respective promoters in brain after MCAO. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS053065-03
Application #
7236053
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Golanov, Eugene V
Project Start
2005-07-13
Project End
2008-07-12
Budget Start
2007-07-13
Budget End
2008-07-12
Support Year
3
Fiscal Year
2007
Total Cost
$50,428
Indirect Cost
Name
Oregon Health and Science University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239