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Estradiol protects white matter of male C57BL6J mice against experimental chronic cerebral hypoperfusion


Dominguez, R and Zitting, M and Liu, Q and Patel, A and Babadjouni, R and Hodis, DM and Chow, RH and Mack, WJ, Estradiol protects white matter of male C57BL6J mice against experimental chronic cerebral hypoperfusion, Journal of Stroke and Cerebrovascular Diseases, 27, (7) pp. 1743-1751. ISSN 1052-3057 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 National Stroke Association

DOI: doi:10.1016/j.jstrokecerebrovasdis.2018.01.030


Background and Purpose: Estradiol is a sex steroid hormone known to protect the brain against damage related to transient and global cerebral ischemia. In the present study, we leverage an experimental murine model of bilateral carotid artery stenosis (BCAS) to examine the putative effects of estradiol therapy on chronic cerebral hypoperfusion. We hypothesize that long-term estradiol therapy protects against white matter injury and declarative memory deficits associated with chronic cerebral hypoperfusion.

Methods: Adult male C57BL/6J mice underwent either surgical BCAS or sham procedures. Two days after surgery, the mice were given oral estradiol (Sham+E, BCAS+E) or placebo (Sham+P, BCAS+P) treatments daily for 31- 34 days. All mice underwent Novel Object Recognition (NOR) testing 31-34 days after the start of oral treatments. Following sacrifice, blood was collected and brains fixed, sliced, and prepared for histological examination of white matter injury and extracellular signal-regulated kinase (ERK) expression.

Results: Animals receiving long-term oral estradiol therapy (BCAS-E2 and Sham-E2) had higher plasma estradiol levels than those receiving placebo treatment (BCAS-P and Sham-P). BCASE2 mice demonstrated less white matter injury (Klüver–Barrera staining) and performed better on the NOR task compared to BCAS-P mice. ERK expression in the brain was increased in the BCAS compared to sham cohorts. Among the BCAS mice, the BCAS-E2 cohort had a greater number of ERK + cells.

Conclusion: This study demonstrates a potentially protective role for oral estradiol therapy in the setting of white matter injury and declarative memory deficits secondary to murine chronic cerebral hypoperfusion.

Item Details

Item Type:Refereed Article
Keywords:estrogen, stroke, ischemia, hypoperfusion, neuroprotection, white matter lesions
Research Division:Biological Sciences
Research Group:Zoology
Research Field:Animal cell and molecular biology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Dominguez, R (Dr Reymundo Dominguez)
ID Code:128006
Year Published:2018
Web of Science® Times Cited:15
Deposited By:Medicine
Deposited On:2018-08-28
Last Modified:2018-09-24

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