Prenatal Undernutrition, Metyrapone, and the Cerebrovasculature

<p>The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, which suggests that fetal stress develops at least in part by fetal overexposure to stress hormones, like glucocorticoids, during gestation. However, few studies have looked at the glucocorticoid hypothesis in the context of blood vessels of the brain. In our first study (cohort 1), pregnant female Sprague-Dawley rats were exposed to 50% maternal undernutrition during the last ten days of gestation. One subgroup was also administered Metyrapone, a corticosterone synthesis inhibitor, during gestation. After delivery, the pups were allowed to grow to maturity at 8-months of age, at which time their middle cerebral arteries were harvested and examined using a combination of vessel bath myography and confocal microscopy. In our second study (cohort 2), pregnant female Sprague-Dawley rats were exposed to Metyrapone (±). On postnatal day 9-10, the rats then underwent Hypoxia-Ischemia (±) (unilateral carotid ligation combined with 1.5 hours 8% hypoxia after 24 hours). The goal of both studies was to determine whether glucocorticoids would increase ischemic vulnerability, an important marker of vascular health. Our results demonstrated that food restriction as well as perturbations to early glucocorticoid exposure are critical to the development of the cerebrovasculature, and that pharmacological glucocorticoid inhibition during gestation can alter the vulnerability to mild hypoxic-ischemic injury. Future studies are currently in progress to determine the ultimate effects of food restriction on the cerebrovasculature during the neonatal period.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2017

Author dc:creator

• Durrant, Lara

Contributors dc:contributor

• Pearce, William J.
• Buchholz, John N.
• Khorram, Omid
• Kirsch, Wolff M.
• Mata-Greenwood, Eugenia
• Zhang, Lubo

• Medical Sciences
• Medicine and Health Sciences
• Physiological Processes
• Physiology
• Nutrition - In Pregnancy; Prenatal Care; Pregnancy - Physiology; Cardiovascular System - Diseases
• Prenatal nutrition disorders; Fetal Origin of Adult Disease; Mytropone; Corticosterone synthesis inhibitor; Vessel bath myography; Confocal microscopy

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/461

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1457