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

Dominguez, R ORCID: 0000-0003-0770-4935, Zitting, M, Liu, Q, Patel, A, Babadjouni, R, Hodis, DM, Chow, RH and Mack, WJ 2018 , 'Estradiol protects white matter of male C57BL6J mice against experimental chronic cerebral hypoperfusion' , Journal of Stroke and Cerebrovascular Diseases, vol. 27, no. 7 , 1743–1751 , doi: 10.1016/j.jstrokecerebrovasdis.2018.01.030.

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Abstract

Background and Purpose: Estradiol is a sex steroid hormone known to protect thebrain against damage related to transient and global cerebral ischemia. In the presentstudy, we leverage an experimental murine model of bilateral carotid artery stenosis(BCAS) to examine the putative effects of estradiol therapy on chronic cerebralhypoperfusion. We hypothesize that long-term estradiol therapy protects againstwhite matter injury and declarative memory deficits associated with chronic cerebralhypoperfusion. Methods: Adult male C57BL/6J mice underwent either surgicalBCAS 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 daysafter the start of oral treatments. Following sacrifice, blood was collected and brainsfixed, sliced, and prepared for histological examination of white matter injury andextracellular signal-regulated kinase (ERK) expression. Results: Animals receivinglong-term oral estradiol therapy (BCAS-E2 and Sham-E2) had higher plasmaestradiol levels than those receiving placebo treatment (BCAS-P and Sham-P). BCASE2mice demonstrated less white matter injury (Klüver–Barrera staining) andperformed better on the NOR task compared to BCAS-P mice. ERK expressionin the brain was increased in the BCAS compared to sham cohorts. Among theBCAS mice, the BCAS-E2 cohort had a greater number of ERK + cells. Conclusion:This study demonstrates a potentially protective role for oral estradiol therapyin the setting of white matter injury and declarative memory deficits secondaryto murine chronic cerebral hypoperfusion.

Item Type: Article
Authors/Creators:Dominguez, R and Zitting, M and Liu, Q and Patel, A and Babadjouni, R and Hodis, DM and Chow, RH and Mack, WJ
Keywords: estrogen, stroke, ischemia, hypoperfusion, neuroprotection, white matter lesions
Journal or Publication Title: Journal of Stroke and Cerebrovascular Diseases
Publisher: W.B. Saunders Co.
ISSN: 1052-3057
DOI / ID Number: 10.1016/j.jstrokecerebrovasdis.2018.01.030
Copyright Information:

Copyright 2018 National Stroke Association

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