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Decreased Glucocorticoid Exposure In Utero Alters Cerebral Artery Development And Reduces Ischemia‐Induced Vascular Injury In The Neonatal Rat Brain

Title: Decreased Glucocorticoid Exposure In Utero Alters Cerebral Artery Development And Reduces Ischemia‐Induced Vascular Injury In The Neonatal Rat Brain
Authors: Durrant, Lara; Jackson, Patsy Naomi; Carreon, Desirelys; Doan, Coleen; Pearce, William
Contributors: National Institutes of Health; National Institute of Neurological Disorders and Stroke
Source: The FASEB Journal ; volume 30, issue S1 ; ISSN 0892-6638 1530-6860
Publisher Information: Wiley
Publication Year: 2016
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: INTRODUCTION Abundant evidence suggests an important role of glucocorticoids (GC) in cerebral injury produced by ischemia, particularly in neonates. The majority of this evidence is focused on the role of GC in neuronal, glial, and endothelial acute responses to injury. In addition to involvement in acute responses, however, GC also play a critical role in cerebrovascular growth and development in utero. Elevation of maternal GC during pregnancy can dramatically alter cerebrovascular structure‐function relations in offspring. The present study examines the hypothesis that depressed glucocorticoid exposure in utero also programs the developing cerebrovasculature, thereby altering the postnatal cerebrovascular responses to ischemia. METHODS The experimental design included four groups: 1) Sham Operated; 2) Ischemia; 3) Sham + Metyrapone; and 4) Ischemia + Metyrapone. Metyrapone (MET), an inhibitor of the enzyme 11‐β hydroxylase that synthesizes corticosterone, was administered in the drinking water at 0.5 mg/ml from day 11 of gestation until birth. At postnatal day 9, rat pups were anesthetized with isoflurane and underwent unilateral carotid ligation, were allowed 24 hours to recover, and then were exposed for 90 minutes to 8% hypoxia. All pups were sacrificed at postnatal days 11–12 after which middle cerebral arteries were harvested for myography and confocal analysis. RESULTS When compared to Sham arteries, ischemia increased passive diameters by up to 25 μm (15%, P
Document Type: article in journal/newspaper
Language: English
DOI: 10.1096/fasebj.30.1_supplement.1275.3
Availability: https://doi.org/10.1096/fasebj.30.1_supplement.1275.3
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
Accession Number: edsbas.52174978
Database: BASE