Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults

Abstract

The ontogeny of regional blood-brain barrier function was quantified with the rate constant for influx (Ki) across the blood-brain barrier with the small molecular weight synthetic, inert hydrophilic amino acid alpha-aminoisobutyric acid (AIB) in chronically instrumented early (87 days of gestation, 60% of gestation) and late (137 days of gestation, 90% of gestation) gestation fetal, newborn (3 days of age), older (24 days of age), and adult (3 years of age) sheep. The Ki was significantly (P < 0.05) lower in the brain regions of the adult sheep and in most brain regions of newborn and older lambs compared with fetuses at 60 and 90% of gestation. The Ki exhibited regional brain heterogeneity (P < 0.05) in the five groups. The patterns of regional heterogeneity were accentuated (P < 0.05) in the younger groups. We conclude that ontogenic decreases in blood-brain barrier permeability are observed in ovine fetuses from 60% of gestation to maturity in the adult.

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

“…Brain vascular volume was determined in three additional separate fetuses and lambs in each group treated under the same protocol with 14 C-polyethylene glycol ( 14 C-PEG, Amersham, England), which was injected intravenously 2 minutes before the end of the study (Stonestreet et al, 2000). The brain vascular volume values did not differ between glucose and 0.5 M NaCl or placebo groups and were similar to reported values (Stonestreet et al, 1996). Brain parenchymal tracer concentration was determined at the end of the experiment.…”

“…Before reaching the threshold, the glucose-induced increases in osmolality resulted in small increases (Figures 1-3) in K i such that barrier function was in the near normal range (Cserr et al, 1987b). It is also important to point out that the changes in K i that we have determined with AIB as the tracer are not dependent on changes in cerebral blood flow because AIB is not a blood flow-dependent substance (Fenstermacher, 1984;Stonestreet et al, 1996).…”

“…Although the BBB exhibited ontogenic decreases in permeability from 60% of gestation to maturity, the barrier was relatively impermeable to AIB at all ages during perinatal development (Stonestreet et al, 1996). Even though we have shown that the BBB is relatively impermeable during development under normal conditions, limited information is available concerning the vulnerability of the BBB to insults and injury during development (Stolp et al, 2005).…”

“…Thus, A br = A m ÀV p c p , where V p is the plasma volume of brain tissue (ml/g) and c p is the concentration of tracer in the terminal plasma sample (dpm/g). V p = A w m /c w p , where A w m and c w p have the same definitions as A m and c p above except that they apply to [ 14 C]-PEG (Cserr et al, 1987b;Stonestreet et al, 1996Stonestreet et al, , 2006. Heart rate, mean arterial blood pressure, amniotic fluid pressures, arterial pH and blood gases, hematocrits, plasma osmolalities, and brain tissue water content values were measured as previously described (Stonestreet et al, 1996(Stonestreet et al, , 2003(Stonestreet et al, , 2004(Stonestreet et al, , 2006.…”

“…We have previously examined the ontogeny of BBB function measured quantitatively with a small hydrophilic molecule, a-aminoisobutyric acid (AIB), during fetal and postnatal development in normal sheep (Stonestreet et al, 1996).…”