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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effects of acute hyperosmolality on blood-brain barrier function in ovine fetuses and lambs

¹Department of Pediatrics, Brown University Medical School, Women and Infants' Hospital of Rhode Island, Providence, Rhode Island; ²Department of Computer Science and Statistics, University of Rhode Island, Kingston, Rhode Island; and ³Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 15 December 2005 ; accepted in final form 28 April 2006

We examined the effects of hyperosmolality on blood-brain barrier (BBB) permeability during development to test the vulnerability of the immature barrier to stress. The BBB response to hyperosmolality was quantified using the blood-to-brain transfer constant (K_i) with -aminoisobutyric acid in fetuses at 60% and 90% gestation, premature, newborn, and older lambs. K_i plotted against osmolality increased as a function of increases in osmolality in all groups and brain regions. The relationship was described (P < 0.05) by a segmented regression model. At lower osmolalities, changes in K_i were minimal, but after a break point (threshold) was reached, the increase (P < 0.05) was linear. We examined the responses of K_i to hyperosmolality within each brain region by comparing the thresholds and slopes of the second regression segment. Lower thresholds and higher slopes imply greater vulnerability to hyperosmolality in the younger groups. Thresholds increased (P < 0.05) with development in the thalamus, superior colliculus, pons, and spinal cord, and slopes of the second regression segment decreased (P < 0.05) in the cerebellum, hippocampus, inferior colliculus, medulla, and spinal cord. BBB resistance to hyperosmolality increased (P < 0.05) with development in most brain regions. The pattern of the K_i plotted against osmolality was (P < 0.05) heterogenous among brain regions in fetuses and premature and newborn lambs, but not in older lambs. We conclude that 1) BBB permeability increased as a function of changes in osmolality, 2) the barrier becomes more resistant to hyperosmolality during development, and 3) the permeability response to hyperosmolality is heterogenous among brain regions in fetuses and premature and newborn lambs.

-aminoisobutyric acid; brain; barrier; development; immature; lambs; mannitol; sheep