title: Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.
abstract: The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.
authors.affiliation: Program in Cell and Molecular Biology, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523-1617, USA.
authors.forename: Krystle A
authors.initials: KA
authors.lastname: Frahm
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Tobet
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000254:growth & development* / Q000473:pathology*; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D008297:Male; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000254:growth & development* / Q000473:pathology*; D020286:Pericytes / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D012737:Sex Factors
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone