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 2018 National Stroke Association
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 Type:||Refereed Article|
|Keywords:||estrogen, stroke, ischemia, hypoperfusion, neuroprotection, white matter lesions|
|Research Division:||Biological Sciences|
|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)|
|Web of Science® Times Cited:||9|
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