title: Comparative effects of glucose- and mannitol-induced osmolar stress on blood-brain barrier function in ovine fetuses and lambs.
abstract: We examined the effects of hyperglycemic hyperosmolality on blood-brain barrier (BBB) permeability during development. We hypothesized that the barrier becomes more resistant to hyperglycemic hyperosmolality during development, and the immature BBB is more resistant to glucose than to mannitol hyperosmolality. We quantified the BBB response to hyperosmolality with the blood-to-brain transfer constant (K(i)) in immature fetuses, premature, and newborn lambs. K(i) increased as a function of increases in osmolality. A segmented regression model described the relationship between K(i) and osmolality. At lower osmolalities, changes in K(i) were minimal but after a threshold, increases were linear. We examined responses of K(i) to hyperglycemic hyperosmolality by comparing the thresholds and slopes of the second regression segments. Lower thresholds and steeper slopes indicate greater vulnerability to hyperosmolality. Thresholds increased (P<0.05) during development in pons and superior colliculus. Thresholds were higher (P<0.05) during glucose than mannitol hyperosmolality in thalamus, superior colliculus, inferior colliculus and medulla of premature lambs, and in cerebrum and cerebellum of newborns. We conclude that BBB permeability increased as a function of changes in glucose osmolality, the barrier becomes more resistant to glucose hyperosmolality in two brain regions during development, and the barrier is more resistant to glucose than to mannitol hyperosmolality in some brain regions of premature and newborn lambs.
authors: Department of Pediatrics, The Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island 02905-240, USA. bstonestreet@wihri.org
authors: Barbara S
authors: BS
authors: Stonestreet
authors: Grazyna B
authors: GB
authors: Sadowska
authors: R Choudary
authors: RC
authors: Hanumara
authors: Mihaela
authors: M
authors: Petrache
authors: Katherine H
authors: KH
authors: Petersson
authors: Clifford S
authors: CS
authors: Patlak
mesh_terms: D000375:Aging / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D002245:Carbon Dioxide / Q000097:blood; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D005865:Gestational Age; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008353:Mannitol / Q000493:pharmacokinetics / Q000494:pharmacology*; D009997:Osmotic Pressure; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis; D012756:Sheep / Q000097:blood* / Q000196:embryology / Q000254:growth & development
chemical_list: D002245:Carbon Dioxide; D008353:Mannitol; D005947:Glucose; D010100:Oxygen